Optimization of Genome Editing Therapeutics for Alzheimer's Disease and Alzheimer's Disease-Related Dementias (AD/ADRD) (U01 - Clinical Trials Not Allowed) | RFA NS 23 017

Opportunity Information: Apply for RFA NS 23 017

The NIH funding opportunity "Optimization of Genome Editing Therapeutics for Alzheimer's Disease and Alzheimer's Disease-Related Dementias (AD/ADRD) (U01 - Clinical Trials Not Allowed)" (Funding Opportunity Number RFA-NS-23-017) is a cooperative agreement designed to move genome editing therapy concepts closer to the point where they can enter formal IND-enabling development. The focus is not on discovering brand-new targets from scratch, but on taking therapeutic leads that already have strong proof-of-concept results in appropriate experimental models and doing the deeper, practical work needed to turn them into realistic drug candidates. In other words, the FOA is aimed at the optimization stage: strengthening the evidence package and refining the therapeutic approach so it is positioned for the kinds of studies required before a first-in-human program could be considered.

A central theme of the announcement is that funded projects should produce an optimized genome editing therapeutic candidate by the end of the project period. That optimized candidate is expected to demonstrate qualities that matter for translation, such as measurable bioactivity (the edit does what it is intended to do), manufacturability (the therapy can be produced in a consistent, scalable way), biodistribution (it reaches the relevant tissues and cell types, especially in the central nervous system where delivery is a major challenge), and evidence of in vivo efficacy and/or clear target engagement. Target engagement is described in a practical way, including measurement of proximal downstream effects, meaning applicants are expected to show that editing the target produces the immediate biological changes that should logically connect to therapeutic benefit. The FOA also highlights the importance of determining optimal dosing, implying a need for dose-ranging work and exposure-response relationships that can support later development decisions.

This announcement is explicitly broad across the Alzheimer's and dementia landscape rather than being restricted to a single diagnosis. It supports genome editing therapeutic development for Alzheimer's disease as well as multiple categories 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). The practical implication is that applicants can propose editing-based strategies relevant to different disease mechanisms across this spectrum, as long as the proposal is grounded in convincing proof-of-concept and focuses on optimization toward an IND-ready package rather than exploratory discovery.

The award mechanism is a U01 cooperative agreement, which typically means NIH program staff have substantial scientific and programmatic involvement compared with a standard research project grant. This structure is often used for milestone-driven, translational efforts where coordination with NIH expectations, go/no-go criteria, and deliverables is important. The FOA also specifies "Clinical Trials Not Allowed," which means the supported work is preclinical or otherwise non-clinical in nature. Applicants should interpret that as a requirement to keep the project centered on candidate optimization and preclinical development activities rather than enrolling human participants in interventional clinical studies.

From an administrative standpoint, the opportunity falls under the health funding activity category and lists CFDA numbers 93.853 and 93.866. The sponsoring agency is the National Institutes of Health. The original closing date provided is 2022-11-30, and the opportunity record shows a creation date of 2022-08-24. The stated award ceiling is $650,000, and while the expected number of awards is not clearly specified in the provided source text, applicants would typically plan budgets and scope around the ceiling and the milestone-oriented nature of a U01.

Eligibility is broad and includes many common public and private applicant types: state, county, and local governments; special district governments; independent school districts; public and state-controlled institutions of higher education; private institutions of higher education; federally recognized Native American tribal governments; tribal organizations (including those other than federally recognized tribal governments); public housing authorities/Indian housing authorities; nonprofits with and without 501(c)(3) status (excluding institutions of higher education in those categories); for-profit organizations other than small businesses; and small businesses. In addition, the FOA calls out a wide set of "other eligible applicants" that NIH often highlights to encourage diverse institutional participation, including Alaska Native and Native Hawaiian Serving Institutions, AANAPISIs, Hispanic-serving institutions, HBCUs, tribally controlled colleges and universities (TCCUs), faith-based or community-based organizations, eligible federal agencies, regional organizations, non-U.S. entities (foreign organizations), and U.S. territories or possessions. The net effect is that the program is open to a wide range of organizations capable of doing advanced genome editing therapeutic optimization, including academic groups, nonprofits, and industry teams, potentially in collaboration.

Taken together, the FOA is best read as a translational push: it is intended for teams that already have a credible genome editing therapeutic lead relevant to AD/ADRD and now need support to refine the candidate and generate the kinds of data that de-risk development. Competitive projects under this announcement would be expected to articulate a clear optimization plan, demonstrate why the current lead is already compelling, and propose rigorous studies that establish delivery and distribution, editing activity and downstream biological impact, performance in relevant in vivo models, manufacturability considerations, and rational dosing strategies, all aligned with the end goal of positioning the candidate for IND-enabling work even though the FOA itself does not fund clinical trials.

• 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 and Alzheimer's Disease-Related Dementias (AD/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 2022-08-24.
• Applicants must submit their applications by 2022-11-30. (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 23 017

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