Part 1. Overview Information

Key Dates

All applications are due by 5:00 PM local time of applicant organization. 

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

No late applications will be accepted for this Notice of Funding Opportunity (NOFO).

It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide, except where instructed to do otherwise (in this NOFO or in a Notice from NIH Guide for Grants and Contracts).

Conformance to all requirements (both in the How to Apply - Application Guide and the NOFO) is required and strictly enforced. Applicants must read and follow all application instructions in the How to Apply - Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the How to Apply - 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. Notice of Funding Opportunity Description

Background

AD is a progressive neurodegenerative disease of the brain and the most common form of dementia in older adults. It is estimated that AD starts 15–20 years before the appearance of the onset of clinical symptoms and ultimately leads to a loss of memory, cognitive skills, and the decline in quality of life in older adults. An estimated 6.5 million Americans aged 65 and older were living with AD in 2022. In response to this public health crisis, the National Alzheimer’s Project Act (NAPA) was signed into law in 2011. As part of the strategic planning process to implement NAPA, NIH AD Research Summits identified research priorities and strategies needed to accelerate basic research.

The progression of AD often follows a predictable temporal and spatial pattern where specific brain regions are affected at different stages of the disease. However, it is unclear why the disease affects certain regions of the brain or why specific cell subpopulations within these brain regions are selectively vulnerable. Several large-scale efforts funded by the National Institute on Aging (NIA) are identifying cell types that are altered in the AD brain by generating high quality single cell transcriptomic and epigenetic datasets in human tissue and model organisms during normal aging and AD progression. These NIA-supported projects have uncovered disease-associated gene signatures across all major brain cell types and have identified subtype-specific alterations in neurons, astrocytes, microglia, oligodendrocytes, and vascular cells in AD. Despite a rapidly growing catalog of brain cell subtype changes in AD progression, it is not clear how these changes contribute to deficits in cell, circuit, or brain function.

Innovative approaches to target and manipulate selectively vulnerable brain cell subtypes could promote breakthroughs in understanding the mechanisms underlying aging and AD/ADRD. Recent advances in technology, supported in-part by the Brain Research Through Advancing Innovative Neurotechnologies® (BRAIN) Initiative, have generated sophisticated tools that enable unprecedented access to specific cell subtypes in the vertebrate animal brain. There have been two major developments in technology that drove this leap in capabilities: 1) adeno-associated viruses (AAV) capsid engineering and 2) cell subclass-specific enhancer element identification. First, the newly engineered AAV capsids can cross the blood-brain barrier in mouse and nonhuman primate and several capsids are biased toward specific brain cell types, such as neurons, astrocytes, oligodendrocytes, or vascular cells. The second major advance arises from high resolution single-cell epigenetics technology, which allows the identification of cell subtype specific enhancer elements that enable refined access to cell subclasses when coupled with AAV transduction. To promote further development of this AAV-enhancer technology, the BRAIN Initiative Armamentarium for Precision Brain Cell Access supports the validation and dissemination of these tools to encourage broad use by the scientific community.

Research Objectives

The aims of this NOFO are to develop novel strategies to target brain cell subtypes implicated in aging and AD/ADRD and implement these tools to address relevant mechanistic hypotheses. This work could lead to breakthroughs in mechanistic research and inform future preclinical studies. To accomplish the aims, this NOFO is soliciting applications that must propose to achieve the following major objectives:

1. Optimize access to brain cell subtypes implicated in aging and AD/ADRD using the following guidelines.
   • Projects must aim to achieve AAV-enhancer in vivo transduction and cell subtype targeting in older and degenerating brain in one or more animal model (rodent, nonhuman primate) of aging of AD/ADRD.
   • To overcome potential barriers and enhance functionality of the AAV vectors, applicants should test different AAV capsids, multiple enhancer elements, and different delivery routes.
   • Applicants should leverage existing multi-omic data (transcriptomics, epigenetics) to identify cell subtypes that likely have a role in aging and/or AD/ADRD, although new datasets may be generated to verify and screen candidate enhancer elements.
   • Projects proposing to optimize this technology for specific cell types where targeting has not been achieved (i.e. microglia) are strongly encouraged.
      
2. Use the optimized AAV-enhancer tools to manipulate and/or monitor brain cell subtypes to address mechanistic hypotheses in aging and AD/ADRD using the following guidelines:
   • Applications must propose to express a transgene to visualize and/or manipulate brain cell subtypes to better understand how they contribute to neurodegeneration.
   • Potential cargos may include calcium/voltage indicators, optogenetic/chemogenetic tools, transcription factors, recombinase elements, tau, or amyloid precursor protein.
   • Possible outcome measurements may be morphology, physiology, connectivity, pathology, behavior, or intracellular signaling pathways.
   • Applications must not propose gene therapy approaches.

R61/R33 Exploratory/Developmental Phased Award Activities

This NOFO utilizes the R61/R33 activity code. Each phase is structured as follows: 

The R61 Phase (Pilot Phase)

The R61 phase is the first phase. This phase provides up to two years of support for pilot activities. This phase supports research projects in which proof-of-principle has not yet been established, and preliminary data may not be available. Thus, the aim of this phase is to acquire sufficient data to demonstrate proof-of-principle.

Proposed projects are expected to be novel, at the conceptual stage, and may involve considerable risk that could lead to a breakthrough in aging and AD/ADRD research.

Applicants are required to submit a plan which includes go/no go criteria, associated milestones, and a timeline for the R61 phase. Milestones appropriate for the R61 phase will depend on the type of research and its stage of development. In the plan, applicants must include the following three steps as go/no-go criteria with specific associated milestones:

1. Identify targets relevant to aging and/or AD/ADRD (i.e., subtypes of neurons, microglia, astrocytes, oligodendrocytes, pericytes).
2. Generate AAV-enhancer vectors and validate cell subtype specificity and selectivity in vitro.
3. Demonstrate effective in vivo brain transduction in a mammalian (rodent and/or nonhuman primate) model of aging and/or AD/ADRD.

Steps 1 through 3 are considered go/no-go criteria. In addition, a timeline (or Gantt chart) including milestones and go/no go criteria is required for all applications. 

R61 milestones must be successfully completed before the R33 phase commences.

The R33 (Implementation Phase)

The R33 phase is the second phase. This phase provides up to three years of support for implementation activities. In this phase, sufficient data should be generated to fully validate the technology in a biologically relevant setting and demonstrate its full utility in addressing biological questions. The R33 implementation phase must demonstrate the specificity of brain cell subtype targeting of the AAV-enhancer tools in vivo and address mechanistic hypotheses related to aging and AD/ADRD in a mammalian model in vivo (rodent and/or nonhuman primate). The research proposed in the R33 phase may include, but is not limited to, the following:

1. Evaluate the in vivo expression profiles of the AAV-enhancer vectors developed in the R61 phase.
2. Demonstrate activity of the cargo such as optical readout of a calcium/voltage indicator, physiological perturbation using an optogenetic/chemogenetic reagent, or genetic knockdown of a target protein.
3. Test hypotheses aimed at understanding the contribution of brain cell subtypes during aging and in the progression of AD/ADRD.

Milestones, Go/No-Go Criteria, and the R61/R33 Transition

Applications must propose a plan which includes go/no-go criteria with a well-defined set of associated milestones for the R61 phase and annual milestones for the R33 phase. At the completion of the R61 phase, the applicant will be required to submit a detailed request to transition to the R33 phase. Specifically, the transition from the R61 to the R33 phase of the award will be administratively reviewed for successful completion of the go/no-go criteria that must be clearly specified in the R61 phase. Applicants can establish go/no-go criteria as they deem fit for their application, but must address each area as described above.

NOTE: Prospective applicants should note that the funding of a grant application for the R61 phase does not guarantee support of the R33 phase. Transition to the R33 phase of the project will occur only if an administrative review process recommends that the R61 planning activities have been successful and the implementation phase of the project can proceed with confidence of success, and if funds are available.

Non-Responsiveness Criteria

The following types of applications will be considered non-responsive to this NOFO and will be administratively withdrawn prior to scientific peer review:  

• Applications that do the following:
  • Propose the use of animal model(s) that are not mouse, rat, or nonhuman primate.
  • Propose gene therapy approaches.
  • Target tissues/organs other than the aging AD/ADRD brain.
  • Propose the development of other unproven, new technologies that do not focus on AAV-enhancer technology.
  • Only use in vitro approaches/organoid cultures.
  • Exclude hypothesis testing.

Available Resources

• Applicants are encouraged, but not limited, to use novel models of AD/ADRD developed by the MODEL-AD Consortium.
• Applicants may consider building on the resources and technology developed by the BRAIN Initiative Armamentarium for Precision Brain Cell Access.

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 NOFO.

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

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations
• Non-domestic (non-U.S.) Entities (Foreign Organizations)

Non-domestic (non-U.S.) Entities (Foreign Organizations) are eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are allowed. 

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the How to Apply - 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. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications for additional information

• 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 registrations; 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 their 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 How to Apply - Application Guide.

2. Cost Sharing

This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement NIH Grants Policy Statement Section 1.2 Definition of Terms.

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 NIH Grants Policy Statement Section 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 NIH Grants Policy Statement 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, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this NOFO. 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 instructions in the Research (R) Instructions in the How to Apply - Application Guide except where instructed in this notice of funding opportunity to do otherwise. Conformance to the requirements in the How to Apply - Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Letter of Intent

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

Erin E. Gray, Ph.D.
Division of Neuroscience
National Institute on Aging (NIA)
Email: [email protected]

Page Limitations

All page limitations described in the How to Apply – Application Guide and the Table of Page Limits must be followed.

The following section supplements the instructions found in the How to Apply – Application Guide and should be used for preparing an application to this NOFO.

SF424(R&R) Cover

All instructions in the How to Apply - Application Guide must be followed.

SF424(R&R) Project/Performance Site Locations

All instructions in the How to Apply - Application Guide must be followed.

SF424(R&R) Other Project Information

All instructions in the How to Apply - Application Guide must be followed.

SF424(R&R) Senior/Key Person Profile

All instructions in the How to Apply - Application Guide must be followed.

R&R Budget

All instructions in the How to Apply - Application Guide must be followed.

R&R Subaward Budget

All instructions in the How to Apply - Application Guide must be followed.

PHS 398 Cover Page Supplement

All instructions in the How to Apply - Application Guide must be followed.

PHS 398 Research Plan

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

Research Strategy
Applications must propose to achieve the following major objectives:

1. Optimize access to brain cell subtypes implicated in aging and AD/ADRD. Projects must aim to achieve AAV-enhancer in vivo transduction and cell subtype targeting in older and degenerating brain in one or more animal model (rodent, nonhuman primate) of aging of AD/ADRD.
2. Use the optimized AAV-enhancer tools to manipulate and/or monitor brain cell subtypes to address mechanistic hypotheses in aging and AD/ADRD. Applications must propose to express a transgene to visualize and/or manipulate brain cell subtypes to better understand how they contribute to neurodegeneration. The R33 implementation phase must demonstrate the specificity of brain cell subtype targeting of the AAV-enhancer tools in vivo and address mechanistic hypotheses related to aging and AD/ADRD in a mammalian model in vivo (rodent and/or nonhuman primate). 

R61/R33 Requirements
Plans for both the R61 and R33 phases must be included, and plans should be clearly delineated in the single Research Strategy attachment. The goals of the R33 phase must be based, in part, on findings collected during the R61 phase. The application must include a unifying and testable hypothesis that transcends both R61 and R33 phases. 

Rationale
Projects are expected to be early-stage and potentially high-risk, and preliminary data on feasibility are not required. However, a sound rationale must be provided as to why the approach proposed is the most appropriate and why it is likely to generate an exceptionally high impact, if successful.

R61 Phase Plan
Applicants are required to submit a plan which includes go/no go criteria, associated milestones, and a timeline for the R61 phase. The specific activities and milestones appropriate for the R61 phase will depend on the type of research and its stage of development. R61 milestones must be successfully completed before the R33 phase commences.

Go/No-Go criteria
Applicants must include the following three steps as go/no-go criteria for the R61 phase with specific associated milestones:

1. Identifying targets relevant to aging and/or AD/ADRD (i.e., subtypes of neurons, microglia, astrocytes, oligodendrocytes, pericytes).
2. Generating AAV-enhancer vectors and validate cell subtype specificity and selectivity in vitro.
3. Demonstrating effective in vivo brain transduction in a mammalian (rodent and/or nonhuman primate) model of aging and/or AD/ADRD.

Proposed Milestones
Milestones conducive to accomplishing the study aims are required for both phases. Milestones must be clearly described, feasible, well-developed, quantifiable, and scientifically justified. The application must include milestones the researchers expect to achieve by the end of the R61 phase, as well as related scientific goals for each year of the R33 phase. A discussion of the milestones relative to the progress of the R61 phase and the implications of successful completion of the milestones for the R33 phase must be included.

Timeline
In addition to the proposed milestones, applications must include a proposed Timeline (or Gantt chart) that describes when key milestones are likely to be met.

R61/R33 Transition
Applications must propose a plan which includes go/no-go criteria with a well-defined set of associated milestones for the R61 phase and annual milestones for the R33 phase. At the completion of the R61 phase, the applicant will be required to submit a detailed request to transition to the R33 phase. Specifically, the transition from the R61 to the R33 phase of the award will be administratively reviewed for successful completion of the go/no-go criteria that must be clearly specified in the R61 phase. Applicants can establish go/no-go criteria as they deem fit for their application, but must address each area as described above.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply - Application Guide.

Other Plan(s): Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages.

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

• 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 Appendix materials are allowed. Follow all instructions for the Appendix as described in the How to Apply - Application Guide.

• No publications or other material, with the exception of blank questionnaires or blank surveys, may be included in the Appendix.

PHS Human Subjects and Clinical Trials Information

When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the How to Apply - 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 Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the How to Apply - 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 How to Apply - Application Guide must be followed.

PHS Assignment Request Form

All instructions in the How to Apply - Application Guide must be followed.

Foreign Organizations

Foreign (non-U.S.) organizations must follow policies described in the NIH Grants Policy Statement, and procedures for foreign organizations described throughout the How to Apply Application Guide.

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

See Part 2. 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. 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). 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 Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications.

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 How to Apply – 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 Section 7.9.1 Selected Items of Cost.

7. Other Submission Requirements and Information

Applications must be submitted electronically following the instructions described in the How to Apply - Application Guide. Paper applications will not be accepted.

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) 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. See Section III of this NOFO for information on registration requirements.

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 How to Apply - 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 and responsiveness by NIA. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

In order to expedite review, applicants are requested to notify the NIA Referral Office by email at [email protected] when the application has been submitted. Please include the FON and title, PD/PI name, and title of the application.

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.

For this particular NOFO, note the following:

This NOFO is for developing or significantly advancing AAV-enhancer approaches during the R61 phase, including proof-of-concept testing. Because projects are expected to be early-stage and potentially high-risk, preliminary data on feasibility are not required. 

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.

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.

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.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by NIA, in accordance with NIH peer review policies and practices, 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 NOFO.

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this NOFO. Following initial peer review, recommended applications will receive a second level of review by the National Advisory Council on Aging. The following will be considered in making funding decisions:

• 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 2.4.4 Disposition of Applications.

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. This request is not a Notice of Award nor should it be construed to be an indicator of possible funding. 

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 NOFO 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: Recipient 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.

2. Administrative and National Policy Requirements

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 Standard Terms and Conditions for Research Grants
• 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.

If a recipient receives an award, the recipient must follow all applicable nondiscrimination laws. The recipient agrees to this when registering in SAM.gov. The recipient must also submit an Assurance of Compliance (HHS-690). To learn more, see the Laws and Regulations Enforced by the HHS Office for Civil Rights website.

HHS recognizes that NIH 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 NOFO.

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 System for Award Management (SAM.gov) requirements. SAM.gov requires Federal agencies to review and consider information about an applicant in the designated integrity and performance system (currently SAM.gov) prior to making an award. An applicant can review and comment on any information in the responsibility/qualification records available in SAM.gov. NIH will consider any comments by the applicant, in addition to the information available in the responsibility/qualification records in SAM.gov, 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 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.

Not Applicable

3. Data Management and Sharing

Consistent with the 2023 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.

4. Reporting

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 NOFOs 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 2 CFR Part 200.301.

The Federal Funding Accountability and Transparency Act of 2006 as amended (FFATA), 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 2 CFR Part 200.113 and Appendix XII to 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 (Responsibility/Qualification in SAM.gov, formerly 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 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: 301-637-3015

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

Erin E. Gray, Ph.D.
Division of Neuroscience
National Institute on Aging (NIA)
Telephone: 301-451-3968
Email: [email protected]
 

Ramesh Vemuri, Ph.D.
National Institute on Aging (NIA)
Telephone: 301-402-7700
Email: [email protected]
 

Robin Laney
National Institute on Aging (NIA)
Telephone: 301-496-1473
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 2 CFR Part 200.