Exploiting Genome or Epigenome Editing to Functionally Validate Genes or Variants Involved in Substance Use Disorders (R21/R33 Clinical Trial Not Allowed) | PAR 19 278

Opportunity Information: Apply for PAR 19 278

This National Institutes of Health (NIH) funding opportunity, PAR 19-278, supports research projects that use modern genome editing or epigenome editing approaches to functionally validate and better characterize genes, genetic variants, or regulatory elements that contribute to substance use disorder (SUD)-relevant traits. The central idea is to move beyond statistical genetic associations and directly test what specific genes or variants actually do in biological systems that model addiction-related processes. By doing so, the program aims to strengthen the evidence linking particular genomic findings to the neurobiology of SUDs and to generate insights that can eventually inform prevention strategies, improved diagnostics, and new therapeutic directions. The announcement is explicitly labeled "Clinical Trial Not Allowed," meaning the supported work should be preclinical, mechanistic, and discovery-focused rather than testing interventions in human participants as clinical trials.

The opportunity uses an R21/R33 phased award structure. In general terms, the R21 phase is intended for early, exploratory, or proof-of-concept work where the key goal is to demonstrate feasibility and produce convincing preliminary evidence that the proposed editing-based strategy can validate the function of the target gene or variant. If the project meets predefined milestones, it can transition to the R33 phase, which supports more extensive validation, characterization, and follow-on experimentation. This structure is meant to reduce risk for high-impact ideas by allowing investigators to establish key technical and biological proof points first, then expand the work once those milestones are met.

Scientifically, the program emphasizes the use of genome editing or epigenome editing to interrogate SUD-related biology in a rigorous, functional way. Genome editing typically refers to directly changing DNA sequence (for example, editing a candidate risk variant to test its causal effect), while epigenome editing refers to targeted manipulation of gene regulation without necessarily changing the underlying DNA sequence (for example, altering chromatin marks or transcriptional control at a locus to determine how regulatory activity influences addiction-relevant phenotypes). The initiative is broadly focused on functional validation and characterization, which can include establishing causal relationships, identifying downstream molecular and cellular consequences, and clarifying how specific genetic perturbations affect phenotypes relevant to substance use, reward circuitry, dependence, withdrawal, craving-like behaviors, stress responsivity, or other addiction-related endpoints that can be modeled experimentally.

A major expectation of the initiative is broad sharing of any genetic resources produced through the funded research. In practical terms, that means if investigators generate edited cell lines, engineered animal models, validated constructs, guide RNAs, or other genomic tools, the program expects those resources to be made widely available to the scientific community. The goal is to accelerate progress across the field by enabling other researchers to use those tools to probe neurobiological mechanisms and to build cumulative knowledge rather than keeping key reagents siloed within individual labs.

The funding instrument is a grant, categorized under education and health, and tied to CFDA number 93.279. The sponsoring agency is NIH. The original posting was created on May 8, 2019, with an original closing date listed as December 17, 2021. The listing does not provide an award ceiling or expected number of awards in the provided source data, so those details would typically need to be confirmed in the full funding announcement or NIH documentation.

Eligibility is broad and includes many types of U.S. organizations, such as 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 that are not federally recognized; 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, where separately listed rules may apply); for-profit organizations (other than small businesses); and small businesses. In addition, the opportunity specifically calls out a wide set of other eligible applicants, including Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISI), Hispanic-serving Institutions, Historically Black Colleges and Universities (HBCUs), Tribally Controlled Colleges and Universities (TCCUs), eligible federal government agencies, faith-based or community-based organizations, regional organizations, U.S. territories or possessions, and non-domestic (non-U.S.) entities (foreign organizations). This broad eligibility is designed to encourage participation from diverse institutional settings and communities, including those historically underrepresented in biomedical research.

Overall, the opportunity is aimed at teams that can combine expertise in genetics, genome/epigenome editing technologies, neuroscience, and addiction biology to produce definitive functional evidence about SUD-related genes and variants. The expected payoff is a stronger mechanistic foundation for understanding how genetic risk translates into brain and behavioral phenotypes relevant to substance use disorders, alongside shared tools and models that help the broader research community move faster toward actionable prevention and treatment advances.

• The National Institutes of Health in the education, health sector is offering a public funding opportunity titled "Exploiting Genome or Epigenome Editing to Functionally Validate Genes or Variants Involved in Substance Use Disorders (R21/R33 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): 93.279.
• This funding opportunity was created on 2019-05-08.
• Applicants must submit their applications by 2021-12-17. (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 PAR 19 278

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