Using Human Cell Animal Chimera Brains to Study HIV Latency and Pathology R01 - Clinical Trials Not Allowed | RFA DA 21 026

Opportunity Information: Apply for RFA DA 21 026

The National Institutes of Health (NIH) funding opportunity RFA-DA-21-026 is an R01 research grant focused on using human cell-animal chimera brain models to better understand HIV latency and HIV-associated brain pathology. The core scientific premise is that newer transplantation methods now make it feasible to engraft human induced pluripotent stem cell (iPSC)-derived primitive neural progenitor cells and/or cord blood-derived microglial progenitor cells into neonatal mice, producing chimeric brains where the human cells survive long term, migrate broadly, differentiate into relevant brain cell types, and become functionally integrated across multiple brain regions. This creates a powerful in vivo platform that sits between traditional mouse models (which lack key human-specific biology) and more limited ex vivo systems like organoids (which do not replicate whole-animal physiology and behavior).

The opportunity is aimed at projects that use these humanized brain chimeras to investigate how HIV infects and persists in the central nervous system. In particular, the announcement highlights studies of HIV infectivity in the brain, proviral activity (how integrated HIV DNA behaves inside infected cells), the formation and maintenance of viral reservoirs in brain-relevant human cells, and mechanisms that drive HIV neuropathogenesis. Because human microglia and neural lineage cells can be represented in these chimeric brains, applicants can ask questions about cell-type-specific susceptibility, the cellular states that support latency, triggers that reactivate latent virus, and the downstream consequences for neural circuitry and brain function. The model is positioned as a way to connect molecular and single-cell observations to network-level outcomes in a living system.

A distinctive emphasis is the ability to study HIV in the context of substance use. The description explicitly notes that these chimeric brain models enable research on HIV and substance abuse comorbidity in an awake, behaving animal, spanning scales from single cells to neural circuits. This implies strong alignment with experiments that combine virology, neuroimmunology, neurobiology, and behavioral neuroscience to understand how substances may alter reservoir dynamics, neuroinflammation, neuronal function, or cognitive and behavioral outcomes tied to HIV infection in the brain.

Administratively, this is a discretionary NIH grant using the R01 mechanism, and it is classified as "Clinical Trials Not Allowed," meaning the supported work must be preclinical and not involve prospectively assigning human participants to interventions to evaluate health-related outcomes. The funding activity category is listed under Education/Health and the CFDA number is 93.279. The opportunity information provided lists an award ceiling of $500,000. The original closing date shown is 2020-11-13, with a creation date of 2020-07-13, indicating this specific solicitation window has passed, although similar topics may reappear in future NIH notices.

Eligibility is broad across U.S.-based organizations and includes state, county, city/township, and 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 and other Native American tribal organizations; public housing authorities/Indian housing authorities; nonprofits with and without 501(c)(3) status (when not institutions of higher education); for-profit organizations (other than small businesses); small businesses; and other eligible entities. The solicitation also calls out additional eligible applicant categories such as 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, regional organizations, eligible federal agencies, and U.S. territories or possessions. Non-domestic (non-U.S.) entities are not eligible to apply, and non-domestic components of U.S. organizations are not eligible; however, "foreign components" as defined in the NIH Grants Policy Statement are allowed, which generally means discrete project elements may be carried out outside the U.S. under NIH rules even though the applicant institution itself must be domestic.

In practical terms, this opportunity is designed for interdisciplinary teams who can build or access humanized neural chimera platforms and then apply modern tools (for example, single-cell genomics, imaging, circuit mapping, and behavioral assays) to answer HIV reservoir and neuropathogenesis questions that are difficult or impossible to resolve in conventional animal models. The NIH is effectively signaling interest in proposals that use these human cell-integrated mouse brains to produce mechanistic, biologically grounded insights into how HIV persists in the brain, what drives neurological damage, and how comorbid substance exposure may worsen or reshape these processes, all within a rigorous preclinical research framework.

• The National Institutes of Health in the education, health sector is offering a public funding opportunity titled "Using Human Cell Animal Chimera Brains to Study HIV Latency and Pathology R01 - 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): 93.279.
• This funding opportunity was created on 2020-07-13.
• Applicants must submit their applications by 2020-11-13. (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 $500,000.00 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 DA 21 026

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