BRAIN Initiative: Development of Novel Tools to Probe Cell-Specific and Circuit-Specific Processes in Human and Non-Human Primate Brain (UG3/UH3 Clinical Trial Optional) | RFA MH 22 115

Opportunity Information: Apply for RFA MH 22 115

The NIH BRAIN Initiative funding opportunity RFA-MH-22-115 supports the development and validation of new research tools designed specifically for studying and influencing cell-specific and circuit-specific activity in the brains of humans and non-human primates. The central idea is to push beyond tools that work well in small, common laboratory species and instead build technologies that can operate effectively in large, complex brains that are closer to human biology. This focus reflects a major bottleneck in neuroscience and medicine: even when scientists can identify dysfunctional brain circuits involved in neurological or psychiatric disorders, it remains difficult to monitor those circuits or change their activity in ways that are safe, precise, and minimally invasive.

This opportunity is a reissue of an earlier announcement (RFA-MH-19-135) and is tied to the broader Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative. It emphasizes that real progress toward new treatments for brain disorders will require tools that can selectively reach and affect the right cells and networks, rather than broadly altering brain tissue. A key motivation is that many emerging intervention strategies, including gene-therapy-like approaches and viral delivery of genetic constructs, are increasingly being considered as potential therapeutic paths for humans. However, translating those strategies into clinical reality requires targeted research to address practical barriers, especially around how to deliver genes, proteins, or other functional payloads into specific brain cell types or circuits reliably and safely in large brains.

The solicitation encourages both genetic and non-genetic tool development. On the genetic side, this can include improved delivery vectors or constructs that make it easier to target particular neuronal or glial cell types, or that allow circuit-level specificity (for example, targeting neurons defined by their connections). On the non-genetic side, it can include new ways to deliver proteins, chemicals, or other agents to precisely defined cells or pathways, as well as technologies that enable finer control, better sensitivity, or more accurate localization than current methods. Across all approaches, the expectation is that the tool or technology is not just proposed conceptually but is developed far enough to demonstrate real utility in the relevant context of human or non-human primate brains.

A defining requirement of strong applications is a clear plan to validate the tool. In practical terms, NIH is signaling that it is not enough to build a platform in isolation; applicants should show how they will test whether it actually works as intended, how well it performs, and why it is an advance over existing options. The validation component is framed as essential because the ultimate goal is to enable detailed analysis and manipulation of complex circuits and to produce insights into cell-to-cell interactions that underlie brain function. This means reviewers will likely look for rigorous performance benchmarks, evidence that the tool can achieve cell-type and/or circuit-level specificity, and a thoughtful pathway for demonstrating reliability and relevance in large-brain systems.

The award mechanism is a cooperative agreement using the UG3/UH3 phased innovation structure, with clinical trial participation listed as optional. In general terms, the UG3 phase is commonly used for an initial milestone-driven development period, and the UH3 phase supports expansion or later-stage activities once early objectives are met, with NIH having substantial programmatic involvement typical of cooperative agreements. While the listing does not provide an award ceiling or an expected number of awards in the provided text, the mechanism and emphasis suggest NIH intends to support projects with clear go/no-go milestones, strong translational logic, and credible validation plans.

Eligibility is broad and includes many types of U.S. and non-U.S. organizations. Applicants may include state, county, and local governments; public and private institutions of higher education; nonprofits with or without 501(c)(3) status; for-profit organizations (other than small businesses) and small businesses; independent school districts; special district governments; public housing authorities/Indian housing authorities; and Native American tribal governments and organizations. The announcement also explicitly highlights additional eligible applicant categories such as Historically Black Colleges and Universities (HBCUs), Hispanic-serving Institutions, Tribally Controlled Colleges and Universities (TCCUs), Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISIs), faith-based or community-based organizations, regional organizations, U.S. territories or possessions, and foreign (non-U.S.) entities. The sponsoring agency is the National Institutes of Health, and the original closing date shown is May 8, 2023. The opportunity is listed under multiple CFDA numbers, reflecting NIH’s multi-institute structure and the cross-cutting relevance of tool-building for neuroscience and brain health.

Overall, this program is aimed at teams that can bridge advanced neurotechnology development with realistic testing in human-relevant brain contexts, especially where precision targeting of specific cells and circuits is the deciding factor. The most competitive proposals are likely to be those that combine technical innovation with a convincing validation strategy and a clear explanation of how the new tool removes a real barrier in large-brain neuroscience and, ultimately, in the translation of circuit-targeted interventions for brain disorders.

• The National Institutes of Health in the education, health, income security and social services sector is offering a public funding opportunity titled "BRAIN Initiative: Development of Novel Tools to Probe Cell-Specific and Circuit-Specific Processes in Human and Non-Human Primate Brain (UG3/UH3 Clinical Trial Optional)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.173, 93.213, 93.242, 93.273, 93.279, 93.286, 93.853, 93.865, 93.866, 93.867.
• This funding opportunity was created on 2022-01-25.
• Applicants must submit their applications by 2023-05-08. (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 MH 22 115

[Watch] Creating a grant proposal using the step-by-step wizard inside the applicant portal: