Noncoding RNAs in Alzheimers Disease and Related Dementias (R21 Clinical Trial Not Allowed) | RFA AG 23 011

Opportunity Information: Apply for RFA AG 23 011

The NIH funding opportunity "Noncoding RNAs in Alzheimers Disease and Related Dementias (R21 Clinical Trial Not Allowed)" (Funding Opportunity Number RFA-AG-23-011; CFDA 93.866) is a discretionary grant program focused on early-stage, exploratory research that digs into how noncoding RNAs (ncRNAs) may contribute to Alzheimer’s disease and related dementias (AD/ADRD). The main purpose is to push the field beyond simple associations by supporting studies that test causality and directionality, figure out mechanisms of action, and evaluate whether specific ncRNAs could realistically serve as therapeutic targets. In practice, the announcement is trying to move ncRNA research from "this RNA changes in disease" to "this RNA helps drive disease biology in a specific way, through a defined pathway, and we can manipulate it."

This FOA uses the NIH R21 mechanism, meaning it is intended for exploratory and developmental projects rather than large, long-term programs. R21 awards are typically used to generate decisive proof-of-concept data, validate a biological hypothesis, and establish feasibility for a bigger follow-on study. Here, that exploratory focus is aimed squarely at functional characterization and mechanistic investigation of ncRNAs that have already been identified in the context of AD/ADRD. The emphasis on "previously identified ncRNAs" signals that applicants should generally not propose purely discovery-driven profiling projects (for example, broad sequencing screens without a clear functional plan). Instead, the expectation is that applicants will start with one or more candidate ncRNAs supported by preliminary evidence and then test what they do, how they do it, and whether changing them alters relevant disease processes.

Scientifically, the announcement centers on several interconnected questions: whether an ncRNA is causal rather than merely correlated with disease; what direction the relationship runs (for instance, whether the ncRNA drives pathology or is a downstream response to neurodegeneration); and which cellular or molecular mechanisms link the ncRNA to AD/ADRD pathogenesis or progression. While the FOA text is brief, the scope implied by these goals is broad and can include many forms of ncRNA biology, such as regulatory functions affecting gene expression, RNA processing, translation, epigenetic regulation, immune signaling, synaptic function, neuronal survival, vascular contributions, or other pathways relevant to dementia. The key is that projects should be mechanistically anchored and designed to produce interpretable functional conclusions.

A notable administrative constraint is that this opportunity is explicitly "Clinical Trial Not Allowed." That means the proposed work cannot include a clinical trial as NIH defines it (a prospective assignment of human participants to an intervention to evaluate health-related outcomes). Applicants can still often work with human-derived materials or data in ways that are not considered a clinical trial, such as analyzing existing datasets, using banked biospecimens, or performing observational analyses, but they must avoid interventional study designs that meet the NIH clinical trial definition. For this FOA, the practical takeaway is that projects should be preclinical and/or mechanistic in nature, with careful attention to study design so it stays outside the clinical trial category.

In terms of who can apply, eligibility is broad and spans many organization types. Eligible applicants include state, county, and city or township 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 other than federally recognized governments; public housing authorities/Indian housing authorities; nonprofit organizations with or without 501(c)(3) status (excluding higher education institutions, which are listed separately); for-profit organizations (other than small businesses); and small businesses. The FOA also highlights a wide range of "other eligible applicants," including Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISIs), Hispanic-serving Institutions, Historically Black Colleges and Universities (HBCUs), Tribally Controlled Colleges and Universities (TCCUs), faith-based or community-based organizations, eligible federal agencies, regional organizations, U.S. territories or possessions, and non-U.S. entities (foreign organizations). That breadth reflects NIH’s interest in drawing in diverse institutions and research environments, including organizations that can contribute specialized expertise, distinctive cohorts or resources, or unique community and translational perspectives.

From a timing and administrative standpoint, the opportunity was created on 2022-02-28 and listed an original closing date of 2022-07-15. The posting does not provide an award ceiling, nor does it state an expected number of awards in the provided source text. Because the funding instrument is a grant and the activity category is health, applicants should expect standard NIH grant application and review processes consistent with R21 submissions, including peer review criteria that emphasize significance, innovation, approach, investigator(s), and environment, with the "approach" section typically carrying major weight for mechanistic and causal claims.

Overall, the opportunity is best understood as a targeted push to translate existing ncRNA leads in AD/ADRD into actionable biology. Competitive applications would usually be expected to (1) start with an ncRNA already linked to AD/ADRD by prior data, (2) propose specific functional experiments that can establish causality and clarify directionality, (3) map the mechanism(s) connecting the ncRNA to disease-relevant pathways or phenotypes, and (4) credibly frame how the findings could support therapeutic development, even if the project itself remains exploratory and non-clinical.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Noncoding RNAs in Alzheimers Disease and Related Dementias (R21 Clinical Trial Not Allowed)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.866.
• This funding opportunity was created on 2022-02-28.
• Applicants must submit their applications by 2022-07-15. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• 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 AG 23 011

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