Optimization of Genome Editing Therapeutics for Alzheimer's Disease-Related Dementias (ADRD) (U01 - Clinical Trials Not Allowed) | RFA NS 24 009

Opportunity Information: Apply for RFA NS 24 009

This funding opportunity, titled "Optimization of Genome Editing Therapeutics for Alzheimer's Disease-Related Dementias (ADRD) (U01 - Clinical Trials Not Allowed)" (RFA-NS-24-009), is a National Institutes of Health (NIH) cooperative agreement intended to move genome editing therapeutic concepts for ADRD closer to the point where they could enter formal IND-enabling development. The central idea is not to fund early discovery or purely exploratory work, but to support projects that already have a credible therapeutic lead backed by convincing proof-of-concept data in appropriate models. The expectation is that applicants come in with something that has demonstrated real promise and then use the award period to rigorously characterize, refine, and optimize that lead so it becomes a realistic candidate for the next major translational steps.

The scope is broad across the ADRD landscape rather than limited to one disease subtype. Projects can target a range of Alzheimer’s disease-related dementias, including frontotemporal dementia (FTD), Lewy body dementias (LBD) such as dementia with Lewy bodies (DLB) and Parkinson disease dementia (PDD), vascular contributions to cognitive impairment and dementia (VCID), and multiple etiology dementias (MED). In practice, this means the program is open to genome editing strategies aimed at different causal mechanisms and genetic or molecular targets, as long as the work is framed as a therapeutic development effort and remains aligned with the goal of generating an optimized, development-ready candidate rather than simply publishing mechanistic findings.

A key feature of this NOFO is its emphasis on optimization milestones that matter for eventual clinical translation. By the end of the project, successful teams are expected to have an optimized genome editing therapeutic candidate supported by data showing bioactivity and a strong link between editing and meaningful biological effects. The NOFO highlights several core areas that applicants are expected to address as appropriate for their modality and indication: manufacturability (whether the therapeutic can realistically be produced with adequate quality and consistency), biodistribution (where the therapy goes in the body and whether it reaches the relevant tissues and cell types), in vivo efficacy (evidence in living systems that the therapy can produce desired effects), and target engagement or measurement of proximal downstream effects (clear readouts showing the edit occurred and is driving the intended near-term biological changes). It also calls for optimization of dosing, which typically includes identifying dose levels and regimens that balance editing efficiency, durability, safety considerations, and therapeutic effect, in a way that matches the intended clinical use.

The award mechanism is a U01 cooperative agreement, meaning NIH is expected to have substantial programmatic involvement compared with a standard research grant. While the NOFO text provided does not spell out all operational details, cooperative agreements commonly involve closer coordination with NIH staff, including agreed-upon milestones, progress tracking, and ongoing scientific and translational input to keep the project aligned with program goals. The NOFO explicitly states that clinical trials are not allowed under this announcement, so the funded activities are preclinical and translational in nature, focused on generating the package of evidence needed to justify and design later-stage development rather than testing an intervention in human participants.

In terms of who can apply, eligibility is expansive across U.S.-based organizations and includes state, county, city, township, and special district governments; public and state-controlled and private institutions of higher education; independent school districts; federally recognized Native American tribal governments and other tribal organizations; public housing authorities/Indian housing authorities; nonprofit organizations with or without 501(c)(3) status (as long as they are not institutions of higher education in the category specified); for-profit organizations other than small businesses; and small businesses. The NOFO also explicitly calls out additional eligible applicant types, including historically Black colleges and universities (HBCUs), Hispanic-serving institutions, tribally controlled colleges and universities (TCCUs), Alaska Native and Native Hawaiian serving institutions, and Asian American Native American Pacific Islander serving institutions (AANAPISIs), as well as faith-based or community-based organizations, eligible federal agencies, regional organizations, and U.S. territories or possessions. At the same time, it draws clear boundaries around foreign participation: non-domestic (non-U.S.) entities and foreign institutions are not eligible to apply, and non-domestic components of U.S. organizations are not eligible. However, foreign components as defined by the NIH Grants Policy Statement are allowed, which typically means a U.S. applicant may include certain well-justified international elements in the project under NIH rules even though a foreign organization cannot serve as the applicant organization.

From the administrative details provided, the opportunity is categorized as discretionary funding and uses a cooperative agreement as the funding instrument. It falls under the NIH health research activity area, with CFDA numbers 93.853 and 93.866. The opportunity was created on 2023-06-26, and the original closing date listed is 2023-11-15. The award ceiling shown is $650,000, which indicates an upper limit per award (commonly per year or per project period depending on the specific NIH budget instructions in the full announcement), and the listing notes expected awards without specifying a number in the excerpt provided.

Overall, the NOFO is essentially a translational bridge for genome editing approaches to ADRD: it is aimed at teams that have already cleared the early proof-of-concept hurdle and now need focused support to refine the candidate into something that looks like a plausible therapeutic product. The program’s success criteria center on generating a well-characterized, optimized genome editing therapeutic candidate with credible in vivo performance, evidence of target engagement and biological activity, practical considerations for manufacturing, and a rational, optimized dosing strategy, all positioned to support the next steps toward IND-enabling work without conducting human clinical trials under this award.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Optimization of Genome Editing Therapeutics for Alzheimer's Disease-Related Dementias (ADRD) (U01 - Clinical Trials Not Allowed)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.853, 93.866.
• This funding opportunity was created on 2023-06-26.
• Applicants must submit their applications by 2023-11-15. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• Each selected applicant is eligible to receive up to $650,000.00 in funding.
• Eligible applicants include: State governments, County governments, City or township governments, Special district governments, Independent school districts, Public and State controlled institutions of higher education, Native American tribal governments (Federally recognized), Public housing authorities/Indian housing authorities, Native American tribal organizations (other than Federally recognized tribal governments), Nonprofits having a 501 (c) (3) status with the IRS, other than institutions of higher education, Nonprofits that do not have a 501 (c) (3) status with the IRS, other than institutions of higher education, Private institutions of higher education, For-profit organizations other than small businesses, Small businesses, Others.

Apply for RFA NS 24 009

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