Part 1. Overview Information

Key Dates

It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Background

The broad applicability of targeted and programmable genome editing approaches, including but not limited to those based on CRISPR-Cas9, raise the possibility of a fundamentally new way to treat a variety of rare genetic diseases as well as numerous therapeutic strategies for common diseases.However, many challenges need to be overcome before such techniques could be widely used in the clinic. A recent NIH Common Fund program, the NIH Somatic Cell Genome Editing (SCGE) Program, supports cross-cutting initiatives to maximize the potential of genome editing technology. One of the initiatives is focusing on creating better animal models for assessing genome editing in vivo and has already produced and validated state-of-art rodent reporter strains to allow the detection of on-target and off-target genome editing in individual cells. Ongoing studies are expected to produce reporter pigs and non-human primates. However, this program is limited to testing new technologies that deliver genome editing machinery developed by program consortium members; furthermore, studies are conducted only in healthy animals, not under disease conditions. While many promising proof-of-concept studies have shown the feasibility of repairing human mutations efficiently and safely in primary cell models, only limited studies have progressed toward an in vivo therapy approach. Additional efforts are needed to address remaining hurdles, to assist SCGE and other NIH gene therapy programs and to provide resources and services to the wider biomedical community. Further investigation is needed to progress from proof-of-concept to real therapy.

Preclinical animal studies and their translation are usually large, expensive and multidisciplinary projects, requiring extensive use, storage and interpretation of animal model phenotypes. These studies also require expert knowledge to choose the best model system for a particular application and interpretation of research results involving a variety of treatment modalities in animals and humans. The ability to produce animals with specific genetic modifications and to replace specific cells and tissues in a variety of species has recently been enhanced dramatically by the development of new technologies, such as nuclease-mediated genome editing and isolation, and the characterization and modification of induced pluripotent stem cells. These advances are helping investigators create cost-effective animal resources with phenotypes more closely analogous to those of human patients in a relatively short period of time. Building animal model resources and services to assist studies and unbiased preclinical evaluation of future genome editing therapeutics in animal models will serve the broader research community interested in translating genome editing to the clinic.

Objectives of this Research Program

The program will establish Testing Centers for Somatic Cell Genome Editing in Animal Models, creating at least one Center for each of specified major mammalian animal model species (rodents, pigs, and non-human primates). The Testing Centers will establish cohorts of wild-type animals, animal disease models, and reporter animals containing one or more reporter genes expressed in all cell types that will allow quantitative evaluation of genome editing in any cell type or disease model of interest. The Testing Centers will develop assays and Standard Operating Procedures (SOPs) for testing new genome editing technologies.The NIH-wide mission of ORIPis to assist NIH Institutes and Centers (ICs) in strengthening existing programs, developing resources, advancing areas of emerging science, and developing new initiatives to move biomedical research forward. Therefore, the proposed studies, models, technologies, and biological materials must be applicable to multiple NIH ICs and should have the capacity to assess approaches for inherited and acquired disorders that impact a range of organ systems and diseases.

The potential ramifications of gene transfer at any age underscores the importance of rigorous assessments of safety in an animal model system which closely recapitulates human development and disease. While all age groups can benefit from such therapies, the youngest patients in need provide unique advantages and opportunities. Since many inherited disorders can be identified prenatally, fetal or neonatal gene transfer may provide the optimal time for treatment as early intervention could eliminate the pathology associated with disease. In addition, the functional immaturity of the fetal or neonatal immune system can overcome the barrier of immune responses that complicates gene transfer in adults. Of particular interest is the development of capacities in the Testing Centers to evaluate in utero gene therapy in animal models and to be able to test a range of therapeutic strategies for tackling a number of devastating genetic conditions, many of which have limited or nonexistent postnatal treatments.

Another objective of the Testing Centers is to enable investigators funded by the NIH to have the opportunity to conduct studies in animal models advancing their translational and preclinical research within a supportive environment that ensures the highest quality standards, rigor, and reproducibility.

Each Testing Center will be expected to:

• Breed and maintain cohorts of well characterized wild-type, reporter and disease model animals in either rodents, pigs, or non-human primates for the testing of delivery vehicles and new editing tools developed by the biomedical community.
• Establish assays and SOPs to evaluate on-target and off-target genome editing in target cells and tissues, including germline cells, and to assess preclinical regulatory requirements (e.g., toxicity, safety, pharmacokinetics, pharmacodynamics, etc.).
• Provide resources and high-quality services to the biomedical community. A basic level of resource maintenance and services as well as a certain number of projects will be supported by grant funds, with the expectation that an additional equal number of projects be supported by fee-for-service.
• Participate in an integrated and collaborative research network across related NIH-funded programs. Data and associated information should be widely shared with the scientific community, while carefully observing established standards. Awardees are expected to comply with the NIH Data Sharing Policy (https://grants.nih.gov/grants/policy/data_sharing/).
• Register catalogs of their resources with current resource tagging and identification initiatives, such as FORCE 11 (https://www.force11.org/group/resource-identification-initiative). These Testing Centers should also encourage and work with investigators to use a resource identification system in their publications and reports.
• Comply with the Public Health Service (PHS) Policy on Humane Care and Use of Laboratory Animals (Policy), and as applicable, with the Animal Welfare Act, and other Federal statutes and regulations relating to animals.

Overall Organization of Testing Center Components

Organization: Each Testing Center will have a multidisciplinary research team of investigators with complementary expertise in using animal models for testing different aspects of genome editing development and pre-clinical applications. A Testing Center will consist of one Coordination Section, and two cores consisting of a Resource Section and a Genome Editing and Biological Effects Testing Section as described below:

• A Testing Center Director [Program Director/Principal Investigator (PD/PI)] will be responsible for scientific leadership and administrative oversight of the Testing Center. The PD/PI (one of the PD/PIs if a multi-PI application) must devote at least 1.2 person months (10%) of effort to the program.
• The Coordination Section will manage and coordinate Testing Center research activities between cores, other program sections, and NIH program staff, and will be responsible for sharing within the Testing Center all sets of data generated by each section or core consistent with achieving the goals of the program. In addition, this section will be responsible for collecting all information on the usage, utility and impact of the Testing Center activities, which will improve the ability of the Center to meet the needs of the biomedical research community.
• The Resource Section will be responsible for archiving germ cells as well as genotyping, breeding and maintenance of cohorts of wild-type, reporter and disease model animals for testing delivery vehicles and new editing tools.
• The Genome Editing and Biological Effects Testing Section will be responsible for testing delivery reagents and genome editing tools. This core will work directly with outside investigators to establish assays and develop SOPs for the detection of genome editing in wild-type, reporter and disease model animals. The core should also develop assays to test the safety of genome editing technologies and delivery systems, including immunogenicity and inflammation. The core should have the appropriate facilities and capabilities to test non-viral and viral vectors, including but not limited to Adenovirus, Adeno-Associated Virus, and Herpes Simplex Virus vectors.
• The Testing Center must have a disaster plan to minimize loss of resources in the event of a catastrophic disaster, such as loss of power, fire, flooding, data breach, or public health crisis.

Testing Centers are required to generate Program Income from distributing models and to offer fee-for-services, thereby recovering a certain percentage of their operating costs. Costs specifically associated with improvement or expansion of the animal resource should be recovered from user fees through a charge schedule acceptable to the NIH. Significant growth of Testing Centers should result from Program Income. Note that the Testing Center’s use of Program Income is governed by the NIH Grants Policy Statement, Section 8.3.2: (http://grants.nih.gov/grants/policy/policy.htm).

Steering Committee: Each Testing Center should have a Steering Committee which will serve as the operational governing board. The Steering Committee should include: the PD(s)/PI(s), Section and Core leads, the NIH Project Scientist (voting), the NIH Program Official (ex officio) and external scientists(s) (if required). Key co-investigators and pre- and post-doctoral trainees, in addition to the PD(s)/PI(s), are eligible to attend Steering Committee meetings (non-voting). An important function of the Steering Committee will be oversight of the research projects for the Center, such as selection of projects and model organisms, expected outcomes and deliverables, and building of resources for the community.

External Advisory Board: An external advisory board should be organized from experts outside of the Testing Center (the required expertise of the members should be stated, but names of the candidates should not be listed) to guide the Testing Center’s leadership in assessing progress and scientific opportunities and to evaluate the progress and effectiveness of interactions among participants as well as the overall contribution of the Testing Center to the genome editing field.

The Testing Centers will attend an annual virtual meeting organized by NIH program to present Center updates and research progress, articulate new opportunities for collaboration, evolve long-term program goals/strategies, as well as plan and strategize communications with the scientific community and relevant NIH ICO program staff. It is expected that the PD/PIs and key personnel will attend these annual meetings.

Program Formation and Governance

The awards funded under this FOA will be cooperative agreements (see Section VI. 2. Cooperative Agreement Terms and Conditions of Award). Close interactions among the awardees and NIH will be required to maintain this complex program. The whole program governance will rest with the Testing Center Steering Committees in collaboration with NIH Program Officials, with advice from the External Advisory Boards providing critical scientific and managerial insights.

See Section VIII. Other Information for award authorities and regulations.

Section II. Award Information

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this FOA.

Section III. Eligibility Information

1. Eligible Applicants

Higher Education Institutions

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions
• Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Local Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)

Federal Governments

• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are not allowed. 

Applicant organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
  • Unique Entity Identifier (UEI) - A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.
• eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants.gov registration; all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov – Applicants must have an active SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account.  PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019. 

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

2. Cost Sharing

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

3. Additional Information on Eligibility

Number of Applications

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

The NIH will not accept duplicate or highly overlapping applications under review at the same time, per 2.3.7.4 Submission of Resubmission Application. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see 2.3.9.4 Similar, Essentially Identical, or Identical Applications).

Section IV. Application and Submission Information

1. Requesting an Application Package

The application forms package specific to this opportunity must be accessed through ASSIST or an institutional system-to-system solution. A button to apply using ASSIST is available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Page Limitations

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

The application should consist of the following components:

• Overall: required (one maximum)
• Coordination Section: required (one maximum)
• The Genome Editing and Biological Effects Testing Section: required (one maximum)
• Resource Section: required (one maximum)

Overall Component

When preparing your application, use Component Type ‘Overall’.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

SF424(R&R) Cover (Overall)

Complete entire form.

PHS 398 Cover Page Supplement (Overall)

Note: Human Embryonic Stem Cell lines from other components should be repeated in cell line table in Overall component.

Research & Related Other Project Information (Overall)

Follow standard instructions.

Facilities and Other Resources Applicants should describe the relevant institutional environments which would facilitate the effective implementation of the proposed program. Applicants should also describe existing or planned resources that would be available to the Testing Center, such as laboratory facilities, participating and affiliated institutions and units, geographic distribution of space and personnel, and consultative and statistical resourcesSpecific names provided for Other Attachments must be no more than 50 characters including spaces.

Project/Performance Site Locations (Overall)

Enter primary site only.

Enter primary site only.

A summary of Project/Performance Sites in the Overall section of the assembled application image in eRA Commons compiled from data collected in the other components will be generated upon submission.

Research and Related Senior/Key Person Profile (Overall)

Include only the Project Director/Principal Investigator (PD/PI) and any multi-PDs/PIs (if applicable to this FOA) for the entire application.

A summary of Senior/Key Persons followed by their Biographical Sketches in the Overall section of the assembled application image in eRA Commons will be generated upon submission.

Budget (Overall)

The only budget information included in the Overall component is the Estimated Project Funding section of the SF424 (R&R) Cover.

A budget summary in the Overall section of the assembled application image in eRA Commons compiled from detailed budget data collected in the other components will be generated upon submission.

PHS 398 Research Plan (Overall)

Specific Aims: List each aim for the Testing Center and how each aim supports the overall objectives of this research program.

Research Strategy:

The Testing Center overview should present a concise overall vision and plan for the proposed Testing Center. This section should describe the framework for the Testing Center, overall strategy and how this strategy will address the objectives of the program, including the impact that results of the proposed Testing Center will have on the development of new innovative technologies and the research field(s) that the Testing Center encompasses. Describe the overall design, development and advancement of the genome editing technology which will be evaluated in animal models and how services will be provided to the wider biomedical community on a national basis.

The application should describe the organization of the proposed Testing Center and its management structure, including integration of the components to maintain efficient operation and the reporting relationships of key personnel. Furthermore, the application should describe how the Testing Center would invite and coordinate activities with NIH funded investigatorsto assess the efficacy and safety of in vivo genome editing and delivery technologies, determine genome editing thresholds for specific diseases associated with minimal off-target effects, and ascertain feasibility parameters in a model system. Additional specific items to be addressed in this section include but are not limited to the following:

• This section should describe services to be provided to the biomedical community, the range of available healthy and disease model animals, as well as general approaches to be used to detect genome editing and evaluate the safety of the genome editing technologies, including duration of genome editing, immunogenicity and inflammation.
• The overall description should demonstrate that the Testing Center will include the necessary expertise to support the team science environment needed to complete the proposed transdisciplinary work. The statement should be brief and avoid duplicating details of the experience and expertise provided in the description of other sections as well as in biosketches. The Testing Center PD/PI (contact PD/PI for applications with multiple PDs/PIs) must be a scientist with a wide range of healthy and disease model animal use experience.
• Applicants should describe how they will work with the Steering Committee to define testing service priorities and the mode of operation that best matches the needs of the biomedical community within broad guidelines of parity, openness, cost-effectiveness, and timeliness, as defined by the Steering Committee, the External Advisory Board, and the NIH.

Letters of Support: Statements of Institutional Commitment, Letters of Support from future users of the resources and services, Letters of Collaborations, and other similar documents, if appropriate, should be included in this attachment (rather than in the other sections).

Resource Sharing Plan:

The following modifications apply:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

• All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan.

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Overall)

When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered “Yes” to the question “Are Human Subjects Involved?” on the R&R Other Project Information form, there must be at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record within the application. The study record(s) must be included in the component(s) where the work is being done, unless the same study spans multiple components. To avoid the creation of duplicate study records, a single study record with sufficient information for all involved components must be included in the Overall component when the same study spans multiple components.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed.

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.

PHS Assignment Request Form (Overall)

All instructions in the SF424 (R&R) Application Guide must be followed.

Coordination Section

When preparing your application, use Component Type ‘Coordination Section.’

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

SF424 (R&R) Cover (Coordination Section)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Coordination Section)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Coordination Section)

Human Subjects: Answer only the ‘Are Human Subjects Involved?’ and 'Is the Project Exempt from Federal regulations?’ questions.

Vertebrate Animals: Answer only the ‘Are Vertebrate Animals Used?’ question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s) (Coordination Section)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Coordination Section)

• In the Project Director/Principal Investigator section of the form, use Project Role of ‘Other’ with Category of ‘Project Lead’ and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget (Coordination Section)

Budget forms appropriate for the specific component will be included in the application package.

The PD/PI (one of the PD/PIs if a multi-PI application) efforts across all components should be a total at least 1.2 person months (10%) of full-time professional effort to the program.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Coordination Section)

Introduction to Application:

The most commonly referenced Research Plan attachments are listed below for your convenience. FOA–specific instructions are required for the Specific Aims and the Research Strategy in each component. FOA-specific instructions are optional for Letters of Support. Delete “Letters of Support” if there are no FOA-specific instructions.

Specific Aims: State concisely the goals and administrative structure of the proposed Coordination Section and how they support the overall objectives of this research program.

Research Strategy:

The application should describe how the Coordination Section will provide multidisciplinary scientific leadership by PDs/PIs who have expertise in the appropriate area of the research activities to be supported by the Testing Center. The application should detail how this Section will effectively coordinate interactions and collaborations of projects, cores and investigators as well as the Program Official. The application should clearly define the management plan for the proposed project, and how this plan will support achievement of the proposed goals and Specific Aims. The application should also describe the plans for evaluation of progress across the Testing Center and communication strategies to manage and track progress of the multiple projects that make up the Testing Center.

The application must describe the plans for customer service and public relations. The plan needs to provide details on how biomedical researchers who are searching for a specific fee-for-service or have specific technical questions about services or animal models will be able to access the Testing Center.

The External Advisory Board should be described; however, board members should not be named in the application and prospective members should not be contacted prior to completion of peer review. Include plans to appoint and convene this group of up to five experts from outside of the Testing Center at least one time per year and to document the Board’s findings and recommendations regarding management strategies and progress tracking as well as the Testing Center's changes in direction or approaches made in response. This information should be included in the regular progress reports submitted to NIH.

The Coordination Section should coordinate participation in Testing Center program evaluation activities, including progress reports and site visits, as well as provide additional communication and materials to ORIP as needed or as requested.It also will collect information on the usage, utility and impact of the Testing Center activities, which will improve the ability of the Center to meet the needs of the biomedical research community.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

Appendix:

Only limited items are allowed in the Appendix.Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Core or Project Name)

When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered “Yes” to the question “Are Human Subjects Involved?” on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.

Genome Editing and Biological Effects Testing Section

When preparing your application, use Component Type ‘Genome Editing and Biological Effects Testing Section.'

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

SF424 (R&R) Cover (Genome Editing and Biological Effects Testing Section)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Genome Editing and Biological Effects Testing Section)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Genome Editing and Biological Effects Testing Section)

Human Subjects: Answer only the ‘Are Human Subjects Involved?’ and 'Is the Project Exempt from Federal regulations?’ questions.

Vertebrate Animals: Answer only the ‘Are Vertebrate Animals Used?’ question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s) (Genome Editing and Biological Effects Testing Section)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Genome Editing and Biological Effects Testing Section)

• In the Project Director/Principal Investigator section of the form, use Project Role of ‘Other’ with Category of ‘Project Lead’ and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget (Genome Editing and Biological Effects Testing Section)

Budget forms appropriate for the specific component will be included in the application package.

The PD/PI (one of the PD/PIs if a multi-PI application) efforts across all components should be total at least 1.2 person months (10%) of full-time professional effort to the program.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Genome Editing and Biological Effects Testing Section)

Introduction to Application:

The most commonly referenced Research Plan attachments are listed below for your convenience. FOA–specific instructions are required for the Specific Aims and the Research Strategy in each component. FOA-specific instructions are optional for Letters of Support. Delete “Letters of Support” if there are no FOA-specific instructions.

Specific Aims: List each aim for the Genome Editing and Biological Effects Testing Section and how these aims support the overall objectives of this research program.

Research Strategy:

State concisely the goals of the proposed Genome Editing and Biological Effects Testing Section and summarize the expected outcome(s), including the impact that the results of this section will exert on the whole Testing Center. The additional specific items to be addressed in this section include but are not limited to the following:

• Services and methodologies for the use of animals to detect genome editing in individual cells of targeted and non-targeted tissues should be described, including positive and negative controls for genome editing to ensure that the results of the studies will be interpretable and will allow valid conclusions about the effectiveness of delivery and genome editing systems.
• Disease models available or that can be acquired if needed at the Testing Center and approaches to study therapeutic effects of the genome editing. Include the range of the methodologies to measure disease phenotypes and to characterize therapeutic treatment windows within stages of disease progression.
• This Section will also be responsible for development of methods to track experiments, document workflows and link this information to databases. During research investigations, large amounts of data from animal models will be collected, for example gene expression, profiling, whole genome sequencing, immunohistochemical data, morphological and imaging data, biochemical analysis etc. Describe how this information will be collected, cross-referenced, analyzed, and investigated to enable a comprehensive overview and development of a hypothesis or hypotheses to drive research activities. Provide preliminary or published data, if available, that support the approaches to be used.
• Describe in detail functional assays and SOPs for evaluation of genome editing in specific cells and tissues in healthy and reporter animals as well as disease models, including evidence of experience with relevant techniques (e.g., immunohistochemistry, fluorescence microscopy, DNA or RNA sequencing).
• Describe in detail plans for testing the safety of genome editing technologies, including at a minimum duration of genome editing activity, inflammation and immunogenicity.
• Provide additional experimental details and methods to validate results and alternative strategies if not successful at first.
• Indicate the Testing Center capacity, including how many animals can be tested and analyzed in a specific time frame.
• Describe plans to increase the rigor and reproducibility of the outcomes (see:https://www.nih.gov/research-training/rigor-reproducibility) whenever appropriate for the model or system being studied; describe approaches, if available, for analyzing potential sex differences or effects in model organisms, particularly if relevant to the potential editing tool applications.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

Appendix:

Only limited items are allowed in the Appendix.Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Genome Editing and Biological Effects Testing Section)

When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered “Yes” to the question “Are Human Subjects Involved?” on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.

Resource Section

When preparing your application, use Component Type ‘Resource Section.’

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

SF424 (R&R) Cover (Resource Section)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Resource Section)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Resource Section)

Human Subjects: Answer only the ‘Are Human Subjects Involved?’ and 'Is the Project Exempt from Federal regulations?’ questions.

Vertebrate Animals: Answer only the ‘Are Vertebrate Animals Used?’ question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s) (Resource Section)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Resource Section)

• In the Project Director/Principal Investigator section of the form, use Project Role of ‘Other’ with Category of ‘Project Lead’ and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget (Resource Section)

Budget forms appropriate for the specific component will be included in the application package.

The PD/PI (one of the PD/PIs if a multi-PI application) efforts across all components should be total at least 1.2 person months (10%) of full-time professional effort to the program.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Resource Section)

Introduction to Application:

The most commonly referenced Research Plan attachments are listed below for your convenience. FOA–specific instructions are required for the Specific Aims and the Research Strategy in each component. FOA-specific instructions are optional for Letters of Support. Delete “Letters of Support” if there are no FOA-specific instructions.

Specific Aims: List each aim for the Resource Section and how these aims support the overall objectives of this research program.

Research Strategy: The application must propose detailed plans describing the design and development of the Resource Section, including capacities of the facilities as well as procedures for acquisition, evaluation, characterization, cryopreservation, and breeding of animal models and of related biomaterials and pathogen screening. The application must describe the design of quality control procedures, data collection, analysis, and verification tests. The application should clarify how the Resource Section will closely collaborate with the Coordination and Genome Editing and Biological Effects Testing Section to provide a user-friendly accounting of the resource’s holdings and ability to support enough appropriate animals for Testing Center activities and services.

Animal strains and biomaterials should be held to the highest standards to optimize reproducibility of studies and assure scientific rigor and transparency; all animals should be thoroughly characterized and documented and include additional quality control measures.

In addition, the Research Strategy must discuss the following areas:

i. The management plan for the proposed Resource Section, and how this plan will support achievement of the proposed aims.

ii. Plans or processes for evaluating and continually maintaining safety regarding biohazards.

iii. Plans or processes for evaluating and maintaining adherence to Health and Human Services and NIH guidelines, policies, and regulations.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

Appendix:

Only limited items are allowed in the Appendix.Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Resource Section)

When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered “Yes” to the question “Are Human Subjects Involved?” on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.

3. Unique Entity Identifier and System for Award Management (SAM)

See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov

4. Submission Dates and Times

Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies) using ASSIST or other electronic submission systems. Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

7. Other Submission Requirements and Information

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.

For information on how your application will be automatically assembled for review and funding consideration after submission go to: http://grants.nih.gov/grants/ElectronicReceipt/files/Electronic_Multi-project_Application_Image_Assembly.pdf.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply – Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) and component Project Leads must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile form. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH.

The applicant organization must ensure that the unique entity identifier provided on the application is the same identifier used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review, NIH. Applications that are incomplete or non-compliant will not be reviewed.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in the policy.

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Reviewers will consider each of the review criteria below in the determination of scientific merit and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Significance

Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

In addition to the standardized criteria above, the following will be evaluated as part of the Significance score for the Overall Component. Does the Testing Center have the potential to serve the needs of investigators in a variety of research areas and will the resources and services the Testing Center provide be available on a national basis? Does the application address important medical problems, and will it help to design and create advanced new therapeutics for human diseases? Was sufficient justification provided to support proposed project activities as a function of the Testing Center?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

In addition to the standardized criteria above, the following will be evaluated as part of the Investigator(s) score for the Overall Component. Does the Testing Center have the necessary expertise to support the team science environment needed to complete the proposed multidisciplinary work?

Innovation

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

In addition to the standardized criteria above, the following will be evaluated as part of the Innovation score for the Overall Component. Does the design of the Testing Center and overall objectives of the program utilize innovative technologies and approaches, which will significantly accelerate application of advances in basic science for medical benefits?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

In addition to the standardized criteria above, the following will be evaluated as part of the Approach score for the Overall Component. Does the design and operating plan provide sufficient range of services for NIH funded investigatorsto assess the efficacy and safety of in vivo genome editing and delivery technologies, determine genome editing thresholds for specific diseases associated with minimal off-target effects, and ascertain feasibility parameters in a model system? Does the project demonstrate a plan for ongoing communication with the Steering Committee to define the testing service priorities and mode of operation that best matches the needs of the biomedical community within broad guidelines of parity, openness, cost-effectiveness, timeliness, as directed by the Steering Committee, the External Advisory Board, and the NIH?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

Additional Review Criteria - The Coordination Section

The Coordination Section will receive a merit descriptor (outstanding, acceptable, unacceptable) for the following:

• Is the proposed administrative structure likely to function effectively in achieving the aims of the Testing Center? Is the management plan well integrated and likely to facilitate achieving Section goals and objectives?
• Do plans for customer service and public relations provide sufficient access to the Testing Center by biomedical researchers who are searching for a specific fee-for-service or have specific technical questions about services or animal models?
• Are plans to solicit External Advisory Board findings and recommendations regarding management strategies and progress tracking as well as the Testing Center's changes in direction or approaches made in response adequate?
• Are details for the Coordination Section activities to coordinate participation in Testing Center evaluation activities, including progress reports and site visits, as well as to provide additional communication and materials to ORIP described?
• Are clear plans for the collection of information on the usage, utility and impact of the Testing Center activities provided?

Additional Review Criteria - Genome Editing and Biological Effects Testing Section

As applicable for the Genome Editing and Biological Effects Testing Section proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

The Genome Editing and Biological Effects Testing Section will receive a merit descriptor (outstanding, acceptable, unacceptable) for the following:

• Are the proposed services and methodology for the use of animals to detect genome editing in individual cells of a variety of targeted and non-targeted tissues, including positive and negative controls for genome editing, enough to ensure that the results of the studies will be interpretable and allow a valid conclusion about the effectiveness of the delivery and genome editing systems?
• Does the application include evidence of experience with relevant techniques?
• Does the Testing Center have a wide range of disease models available or have adequate plans to acquire them if needed?
• Does the Testing Center described in sufficient details the range of methodologies to measure disease phenotypes and to characterize therapeutic treatment windows within particular stages of disease progression?
• Are plans for tracking of experiments and collecting data from animal models (for example gene expression, profiling, whole genome sequencing, immunohistochemical data, morphological and imaging data, biochemical analysis, etc.) sufficient to provide a comprehensive overview and development of a hypothesis or hypotheses to drive research activities?
• Are experimental details of functional assays and SOPs for evaluation of genome editing in specific cells and tissues in healthy and reporter animals as well as disease models, including evidence of experience with the relevant techniques (e.g., immunohistochemistry, fluorescence microscopy, DNA or RNA sequencing) presented?
• Are Testing Center capacities and number of animals which will be available for testing described?
• Are plans described to increase the rigor and reproducibility of outcomes and approaches for analyzing potential sex differences or effects in model organisms, particularly if relevant to the potential editing tool applications?

Additional Review Criteria - Resource Section

As applicable for the Resource Section proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

The Resource Section will receive a merit descriptor (outstanding, acceptable, unacceptable) for the following:

• Are the goals of the proposed Resource Section and the expected outcome(s) reasonable and achievable, including the impact that proposed Resource Section capacities will exert on Testing Center services?
• Are strategies described adequate to reach project goals for acquisition, evaluation, characterization, cryopreservation, and breeding of animal models and of related biomaterials and pathogen screening?
• Are mechanisms provided to ensure the highest standards to optimize reproducibility of studies and assure scientific rigor and transparency? Do they allow thorough characterization and document quality control measures for animal models?

Protections for Human Subjects

For research that involves human subjects but does not involve one of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

Inclusion of Women, Minorities, and Individuals Across the Lifespan

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animals Section.

Biohazards

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

Not Applicable

Renewals

Not Applicable

Revisions

Not Applicable

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

Applications from Foreign Organizations

Not Applicable

Select Agent Research

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Resource Sharing Plans

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3) Genomic Data Sharing Plan (GDS).

Authentication of Key Biological and/or Chemical Resources:

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

Budget and Period of Support

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the Center of Scientific Review, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications will receive a written critique.

Applications may undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.

Appeals of initial peer review will not be accepted for applications submitted in response to this FOA

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

Section VI. Award Administration Information

1. Award Notices

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the recipient's business official.

Recipients must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

Prior Approval of Pilot Projects

Recipient-selected projects that involve {clinical trials or studies involving greater than minimal risk to human subjects} require prior approval by NIH prior to initiation.

• The recipient institution will comply with the NIH Guidance on Changes That Involve Human Subjects in Active Awards and That Will Require Prior NIH Approval.
• The recipient institution will provide NIH with specific plans for data and safety monitoring, and will notify the IRB and NIH of serious adverse events and unanticipated problems, consistent with NIH DSMP policies.

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities, including of note, but not limited to:

• Federalwide Research Terms and Conditions
• Prohibition on Certain Telecommunications and Video Surveillance Services or Equipment
• Acknowledgment of Federal Funding

If a recipient is successful and receives a Notice of Award, in accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

Should the applicant organization successfully compete for an award, recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex (including a gender identity, sexual orientation, and pregnancy). This includes ensuring programs are accessible to persons with limited English proficiency and persons with disabilities. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html https://www.hhs.gov/civil-rights/for-individuals/nondiscrimination/index.html.

HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA.

Recipients of FFA must ensure that their programs are accessible to persons with limited English proficiency. For guidance on meeting the legal obligation to take reasonable steps to ensure meaningful access to programs or activities by limited English proficient individuals see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/fact-sheet-guidance/index.html and https://www.lep.gov.

• For information on an institution's specific legal obligations for serving qualified individuals with disabilities, including reasonable accommodations and making services accessible to them, see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html.

• HHS funded health and education programs must be administered in an environment free of sexual harassment, see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html; For information about NIH's commitment to supporting a safe and respectful work environment, who to contact with questions or concerns, and what NIH's expectations are for institutions and the individuals supported on NIH-funded awards, please see https://grants.nih.gov/grants/policy/harassment.htm.

• For guidance on administering programs in compliance with applicable federal conscience protection and associated anti-discrimination laws see https://www.hhs.gov/conscience/conscience-protections/index.html and https://www.hhs.gov/conscience/religious-freedom/index.html.

Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 and 2 CFR Part 200.206 “Federal awarding agency review of risk posed by applicants.” This provision will apply to all NIH grants and cooperative agreements except fellowships.

The following special terms of award are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS grant administration regulations at 45 CFR Parts 75 and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the recipients is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the recipients for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

The PD(s)/PI(s) will have the primary responsibility for:

• Leading the project as a whole, and agreeing to accept close assistance, advice, coordination, and collaborate with the ORIP Project Scientist and other Center awardees.
• Planning, direction, and execution of the proposed project will be solely that of the PD(s)/PI(s). They will determine experimental approaches, design protocols, set project milestones and conduct experiments.
• Participating in group activities, including the Steering Committee, to share design and analysis techniques and promote comparability across studies wherever possible.
• Ensuring active participation of collaborators in group activities, if applicable.
• Effecting Steering Committee recommendations for designing, implementing, evaluating, and disseminating demonstration disease modeling research projects, as appropriate and feasible.
• Adhering to the general NIH policies regarding sharing resources, data release, and resource sharing, as well as the specific data and resource-sharing policies proposed in the application, as modified by any negotiation prior to award.
• Submitting periodic progress reports in a standard format, as agreed upon by NIH program staff.
• Attending and participating in Steering Committee meetings and accepting and implementing the guidelines and recommendations, as appropriate.
• Ensuring that Testing Center representatives will meet yearly at a virtual meeting organized by NIH program staff.

Recipients will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies.

An NIH Project Scientist will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

The Project Scientist is an NIH staff member who will have substantial scientific and programmatic involvement during the conduct of this activity through technical assistance, advice, and coordination. However, the role of NIH staff will be to facilitate and not to direct the activities. It is anticipated that decisions in all activities will be reached by consensus of the program, and NIH staff will be given the opportunity to offer input to this process. The Project Scientist will participate as a member of the Steering Committee and will have one vote. The Project Scientist will have the following substantial involvement:

• Participate with the other Steering Committee members in the group process of setting research priorities, deciding optimal research approaches and protocol designs, and contributing to the adjustment of research protocols or approaches as warranted. The Project Scientist will assist and facilitate the group process and not direct it.
• Serve as a liaison, helping to coordinate activities among and for the Center awardees, including acting as a liaison to the NIH, and as an information resource for the Center awardees about other research activities. The Project Scientist will also coordinate the efforts of the program with other groups conducting similar studies.
• Attend all Steering Committee meetings as a voting member and assisting in developing operating guidelines, quality control procedures, and consistent policies for dealing with situations that require coordinated action. The Project Scientist will be responsible for working with the Coordinating Section as needed to manage the logistical aspects of the program.
• Report periodically on the progress of the program to the ORIP and DCM Directors.
• Retain the option to recommend withholding or reduction of support from any project that fails to achieve its goals or comply with the Terms and Conditions of award.
• Serve as a liaison between the Steering Committee and the External Advisory Board, attend External Advisory Board meetings in a non-voting liaison member role, and arrange for timely preparation and distribution of meeting minutes.
• Provide advice in the management and technical performance of the award.
• Assist in promoting the availability of the data and related resources developed in the course of this program to the scientific community at large.
• Participate in data analyses, interpretations, and, where warranted, co-authorship of the publication of results of studies conducted through the program.

Other NIH staff may assist the recipients as designated by the Program Official.

Additionally, an NIH Program Official will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. The Program Official may withhold or reduce support from any recipient that fails to achieve its goals or comply with the Terms and Conditions of Award. The assigned program official may also serve as an NIH Project Scientist.

The Steering Committee will:

• Participate in monitoring "day to day" scientific progress of the research project plan as well as assess recruitment and progress of the milestones.
• Convene monthly video or audio teleconferences and yearly in person or hybrid meetings to monitor progress on the research project plan and to address issues or activities that impact the project. Identify areas of shared interest and potential for collaboration.
• Establish workgroups for specific tasks as the Steering Committee deems appropriate.

Areas of Joint Responsibility include:

Close interaction among the participating investigators will be required, as well as significant involvement from the NIH, to develop appropriate strategies and tools to test new therapeutics. The Center awardees, Project Scientist, and Steering Committee will meet at least one time per year and monthly on conference calls as needed to share information on data resources, methodologies, analytical tools, as well as data and preliminary results. Key co-investigators and pre- and postdoctoral trainees, especially those who are members of under-represented minority groups or those from different but related disciplines, in addition to the PIs, are eligible to attend these meetings.

The Steering Committee will be responsible for coordinating the activities being conducted by the program. The Steering Committee membership will include one NIH Project Scientist and the PD/PI from each Center Section. The Steering Committee may add additional members, and other government staff may attend the Steering Committee meetings as desired.

To address particular issues, the Steering Committee may establish working groups as needed, which will include representatives from the program and the NIH and possibly other experts.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to arbitration. An Arbitration Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special arbitration procedure in no way affects the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulations 42 CFR Part 50, Subpart D and HHS regulations 45 CFR Part 16.

3. Data Management and Sharing

Note: The NIH Policy for Data Management and Sharing is effective for due dates on or after January 25, 2023.

Consistent with the NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described.

When multiple years are involved, recipients will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement. NIH FOAs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 45 CFR Part 75.301 and 2 CFR Part 200.301.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for recipients of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All recipients of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over the threshold. See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 45 CFR 75.113and 2 CFR Part 200.113 and Appendix XII to 45 CFR Part 75 and 2 CFR Part 200, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM)about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75and 2 CFR Part 200 – Award Term and Condition for Recipient Integrity and Performance Matters.

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)

Finding Help Online: https://www.era.nih.gov/need-help  (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-480-7075

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]

Oleg Mirochnitchenko, Ph.D.
Office of Research Infrastructure Programs (ORIP)
Telephone: 301-435-0749
Email: [email protected]

Elkena Smirnova, Ph.D.
Center for Scientific Review (CSR)
Email: [email protected]

Cen

Donna James
NHLBI Office of Grants Management, ORIP Team
Telephone: 301-827-8063
Email: [email protected]

Section VIII. Other Information

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75 and 2 CFR Part 200.