The National Institute on Drug Abuse (NIDA) invites applications for the "Functional Validation and/or Characterization of Genes or Variants Implicated in Substance Use Disorders (SUDs)" initiative, which aims to advance understanding of the genetic and molecular basis of addiction by functionally validating or characterizing genes and genetic variants associated with SUDs. This Notice of Funding Opportunity (NOFO) encourages research utilizing innovative genomic and genome-editing approaches to identify addiction-relevant genes, variants, and pathways. These studies are essential for the discovery of new therapeutic targets to prevent or treat addiction. Applicants may employ various model organisms, genetic manipulation techniques, and high-throughput methodologies to investigate addiction-linked genetic and epigenetic factors.

This NOFO is structured as a phased R21/R33 award, with an initial R21 phase supporting high-risk, high-reward projects that validate candidate genes or variants for addiction relevance. Successful R21 projects, contingent on achieving predefined milestones, may transition to an R33 phase for in-depth functional studies. During the R33 phase, researchers will focus on behavioral, molecular, and neurobiological characterization of validated genes or variants in models such as rodents, zebrafish, human organoids, or other appropriate systems. Each application should outline specific milestones (Go/No Go criteria) for the R21 phase that will be evaluated to determine eligibility for the R33 phase.

Eligible organizations include higher education institutions, nonprofits, for-profit organizations, government entities, and foreign institutions. The R21 budget may not exceed $125,000 annually in direct costs, while the R33 phase allows for up to $250,000 annually, with a maximum project period of five years. Applicants must submit their applications through electronic systems such as ASSIST or Grants.gov Workspace by the due dates: March 3, 2025, and July 28, 2025. A letter of intent is encouraged 30 days before the application due date.

Key considerations for applicants include demonstrating a team with expertise in addiction science, providing clear justification for the genetic targets chosen, and ensuring access to advanced genomic manipulation technologies. Functional studies should incorporate exposure to substances of abuse relevant to NIDA’s mission, excluding alcohol, which is addressed by separate funding opportunities. Additionally, applicants should not propose to develop transgenic models already available through resources like the Knockout Mouse Project (KOMP).

The application review will assess scientific merit based on significance, innovation, approach, rigor, feasibility, and the expertise of the research team. Resource sharing is essential; all genetic resources developed must be made publicly accessible, aligning with NIDA’s commitment to advancing addiction research. Final award decisions will be based on scientific merit, funding availability, and alignment with NIDA priorities.

Applications will undergo scientific peer review, with decisions for R33 phase advancement based on successful completion of R21 milestones, peer review feedback, and programmatic priorities. Contact information for technical, financial, and scientific inquiries is provided in the NOFO, and all applications must follow NIH policies for human subjects, vertebrate animals, and data sharing requirements. This funding opportunity supports the development of genetic resources and knowledge essential to addressing the complexities of SUDs and expanding potential therapeutic pathways.