Key Dates

Related Announcements

NOT-RM-23-008 - Notice of Upcoming Prize Competition Announcement for the TARGETED (Targeted Genome Editor Delivery) Challenge

RFA-RM-18-016 Innovative Technologies to Deliver Genome Editing Machinery to Disease-relevant Cells and Tissues (UG3/UH3 Clinical Trial Not Allowed)

RFA-RM-18-023 Innovative Technologies to Deliver Genome Editing Machinery to Disease-relevant Cells and Tissues (UG3/UH3 Clinical Trial Not Allowed)

RFA-RM-22-014 Technologies and Assays for Therapeutic Genome Editing INDs (U01, Clinical Trial Not Allowed)

RFA-RM-22-015 IND-enabling Studies of Somatic Genome Editing Therapeutic Leads (U19, Clinical Trial Not allowed)

RFA-RM-22-016 Platform Clinical Trials of Somatic Genome Editing for Multiple Diseases (UG3/UH3, Clinical Trial Required)

RFA-RM-22-017 Somatic Cell Genome Editing Translational Coordination and Dissemination Center (U24, Clinical Trial Not Allowed)

Issued by

Office of Strategic Coordination (Common Fund)

Purpose

This Notice is a time-sensitive Request for Information (RFI) inviting comments and guidance to be considered during the development of a prize competition to advance delivery technologies that fully realize the promise of somatic genome editing to reduce disease burden.

Background

The NIH Somatic Cell Genome Editing (SCGE) program is funded through the NIH Common Fund, which supports cross-cutting programs that are expected to have exceptionally high impact. All Common Fund initiatives invite investigators to develop bold and innovative approaches to address problems that may seem intractable or to seize new opportunities that offer the potential for transformation of research processes.

The simplicity and 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 diseases. However, many challenges need to be overcome before such techniques could be widely used in the clinic. To maximize the potential of genome editing technology, the SGCE program was developed to accelerate the translation of somatic genome editing technology into clinical applications.

The first phase of the SCGE program funded 45 projects, including 20 projects developing novel or improved delivery systems for the delivery of editors into somatic cells. Based on input received from stakeholders from academia, industry, and regulatory agencies, as well as the substantial progress in the field of genome editing since the launch of the first five-year phase of the SCGE program, the second five-year phase of SCGE will focus on translating and accelerating safe and effective genome editing therapeutics into the clinic. However, it is possible that there are gaps of significant strategic importance in the landscape of delivery technologies that merit additional SCGE program investment during Phase 2 of the SCGE program.

The prize mechanism, wherein solvers generate solutions in a prize competition, may be appropriate for addressing such gaps. Section 2002 "Eureka Prize Competitions" of the 21st Century Cures Act, enacted on December 13, 2016 (P.L. 114-255), requires NIH to support and report on prize competitions in areas of biomedical science that could: 1) realize significant advancements and 2) improve health outcomes in human diseases and conditions that have a disproportionately small research investment relative to expenses for prevention and treatment, represent a serious and significant disease burden, or for which there is potential for significant return on investment. Section 2002 prize competitions, like other NIH prize competitions, must be carried out pursuant to NIH’s existing prize authority, i.e., the America COMPETES Act (P.L. 111-358), as revised by the American Innovation and Competitiveness Act (P.L. 114-326).

The SCGE program is considering a potential multi-phase prize competition to spur development of new, transformative delivery technologies, and anticipates that information received in response to this RFI could help design and structure the competition phase(s) of a prize competition.

Information Requested

This RFI seeks input from stakeholders throughout the scientific research community and the general public. We hope to receive concise input that would help us create a feasible, equitable, and successful prize competition that triggers development of ambitious technologies with strategic capabilities. The SCGE program is considering ways to best structure a potential prize competition, and anticipates that information received in response to this RFI would help inform the prize competition planning and ensure participants have adequate time to develop and test ambitious, novel gene delivery systems. We hope to receive comments that will help us create judging process and criteria that is consistent, realistic, fair, easily understood and easily applied. For more information on the prize competition format and currently active prize competitions, commenters may wish to visit challenge.gov.

Individuals wishing to comment on the potential prize for transformative genome editor delivery technologies may consider providing feedback on the following topics, or any other idea that a commentor would like to suggest:

Strategic Gaps in Delivery Technologies for Somatic Cell Genome Editing

• Input about gaps of strategic importance in the landscape of delivery technologies that a prize competition could address, e.g.:
  • A highly efficient non-viral delivery system capable of crossing the blood brain barrier to deliver genome editing machinery to a majority of all cell types in the CNS
  • Programmable delivery systems that could target specific tissues or cell types (e.g., stem cells)
  • Other gaps in the delivery system landscape, that are also of strategic importance. Comments may be submitted in any area of gene delivery or gene editing technologies.
• Existing solutions for targeting delivery systems (RNPs, LNPs, peptide shuttles, polymer formulations, etc.) to cells of interests
• Comments on strategies to overcome biological barriers to gene delivery at the host/organ/tissue level including but not limited to:
  • tissue trapping, mitigating nonspecific interactions at the cell surface to enhance cell-specific targeting immunogenicity,
  • penetration of endothelial layers or other tissue barriers,
  • delivery to epithelia with natural barriers such as mucus (gut, lung, etc.),
  • stability of delivery reagents in local environment until they reach intended target tissue/cells, and
  • delivery to tissues less well perfused than the liver (lung, skin, brain, etc.).
• Comments on strategies to overcome cellular barriers of gene delivery including but not limited to:
  • mitigating nonspecific interactions at the cell surface to enhance cell-specific targeting,
  • improving cellular uptake & endocytosis,
  • improving intracellular trafficking of editing cargo,
  • preventing degradation in lysosomes,
  • reducing physical/metabolic barriers in the cytosol to enhance nuclear delivery, and
  • uptake of editing machinery.
• Comments on strategies to avoid editing in germ cells, consistent with NIH support of an international moratorium on germline editing https://www.nih.gov/about-nih/who-we-are/nih-director/statements/nih-supports-international-moratorium-clinical-application-germline-editing

Structure of the Prize Competition

• The feasibility and structure of a prize competition, whether a prize competition would be better suited for a multi-phased approach (e.g., proposal and research phases, see challenge.gov for examples) or for a single phase, and the appropriate length of time for the phase(s).
• Appropriate milestones within the challenge (e.g., preliminary/pilot results, necessary models are in place, external validation of results, etc.), reasonable timeframes for completing these milestones, and whether additional points should be given to entrants who complete milestones on time
• Time needed to develop a solution at different stages of maturity (e.g. time to develop ideas for promising, novel approaches, preliminary in vitro or in vivo data and/or reproduceable data in animal models) and for judges to identify one or more winners
• Minimal dollar amount for the award, that would make the prize competition attractive to potential solvers submitting solutions at different stages of maturity (e.g., ideas for promising, novel approaches, preliminary in vitro or in vivo data and/or reproduceable data in animal models)
• Intellectual property (IP) considerations to maximize the number of interested solvers, while promoting broad utility of a successful technology that result from the program.
• IP strategies for promoting the utility and rapid clinical application of successful solutions for diseases so rare that they have never attracted commercial interest
• Other suggestions for how a challenge could be structured to best facilitate fair and open competition and to best allow for solutions to be successful

Outreach Landscape

• Methods of communication and types of media that would be helpful to share information about the prize competition to researchers and entrepreneurs, from groups that are underrepresented in relevant scientific areas, and others who could be part of the applicant pool
• Attractiveness of a prize competition to a broad audience of possible solvers
• Duplication with other ongoing activities
• Ways to best disseminate successful solutions of the prize competition

Judging Criteria

• Suggestions on the background and expertise of individuals to include as prize competition judges. (For example, industry leaders, government officials, peers, etc.)
• Examples of metrics that judges might use to identify a winner, and whether certain metrics should be weighted more than others during judging
• If milestones are used during the competition phase of the challenge prize, whether timely completion/achievement of the milestones should be considered during judging
• Ways to resolve potential scoring ties between multiple solutions

Reasons and Potential Barriers to Participating in Prize Challenge

• Major factors or other reasons that may influence an individual’s decision to compete in the potential prize competition described in this information request
• Major barriers that may impede applying for the potential prize described in this request, e.g. resource limitations, familiarity with prize competitions, sufficient notice of opportunity, appropriate collaborators, IP considerations. Comments may reflect considerations about what potential solutions, if any, may be available to overcome such barriers.

Submitting a Response

All comments must be submitted via email as text or as an attached electronic document to [email protected]. Your responses should be submitted by June 17^th, 2022. The suggested response length is up to 1500 words. It is not necessary to comment on all of the potential topics described above. The submitted information will be reviewed by NIH staff.

Responses to this RFI are voluntary. Do not include any proprietary, classified, confidential, trade secret, or sensitive information in your response. The responses will be reviewed by NIH staff, and individual feedback will not be provided to any responder. The Government will use the information submitted in response to this RFI at its discretion. The Government reserves the right to use any submitted information on public NIH websites, in reports, in summaries of the state of the science, in any possible resultant solicitation(s), grant(s), or cooperative agreement(s), or in the development of future funding opportunity announcements.

This RFI is for information and planning purposes only and shall not be construed as a solicitation, grant, or cooperative agreement, or as an obligation on the part of the Federal Government, the NIH, or individual NIH Institutes and Centers to provide support for any ideas identified in response to it. The Government will not pay for the preparation of any information submitted or for the Government’s use of such information. No basis for claims against the U.S. Government shall arise as a result of a response to this request for information or from the Government’s use of such information.

We look forward to your input and hope that you will share this RFI document with your colleagues.

Inquiries

Please direct all inquiries to:

Somatic Cell Genome Editing Program

Email: [email protected]