Modeling HIV Neuropathology Using Microglia from Human iPSC and Cerebral Organoids (R01 Clinical Trial Not Allowed) | RFA DA 20 023

Opportunity Information: Apply for RFA DA 20 023

The grant opportunity titled "Modeling HIV Neuropathology Using Microglia from Human iPSC and Cerebral Organoids (R01 Clinical Trial Not Allowed)" (Funding Opportunity Number RFA-DA-20-023) is a National Institutes of Health (NIH) research grant solicitation that focuses on HIV-associated neurological disorders (HAND) in the modern treatment era. Even though combination antiretroviral therapy (cART) has dramatically improved survival and systemic viral control, many people living with HIV continue to experience persistent neurological and cognitive complications. This FOA is designed to push the field toward a clearer, mechanistic understanding of why HAND continues under long-term cART, with an emphasis on the brain’s immune environment and how it is altered over time.

A central feature of this FOA is the use of patient-derived induced pluripotent stem cells (iPSCs) to create human microglia-like cells (often referred to as induced microglia) and cerebral organoids. Microglia are the resident immune cells of the central nervous system and are increasingly recognized as key drivers of neuroinflammation, synaptic changes, and neuronal injury. Cerebral organoids, meanwhile, provide a three-dimensional, human-relevant model that can capture aspects of brain development, cell-cell interactions, and tissue-like organization that are difficult to reproduce in standard cell culture. The FOA encourages applications that combine these model systems to investigate cellular and molecular pathways involved in HAND, especially in contexts that reflect long-term antiretroviral exposure and the chronic, low-level inflammatory and immune signaling thought to persist in treated HIV.

The research scope is explicitly mechanistic, aiming to delineate neuropathophysiology at the cellular and molecular level. Applicants are expected to leverage iPSC-derived microglia and cerebral organoids to probe questions such as how microglial activation states are shaped by HIV-related factors in treated individuals, how chronic immune signaling impacts neuronal health and network function, and what molecular programs or signaling cascades might explain ongoing neurocognitive impairment despite viral suppression. The FOA is positioned to support studies that can connect changes in microglial biology to downstream effects in neural circuits, synaptic integrity, myelination processes, or neurotoxic inflammatory environments, using human-derived experimental systems that are closer to patient biology than many animal or immortalized cell models.

This is an R01 mechanism, meaning it supports substantial, hypothesis-driven research projects rather than small pilot studies. The FOA specifies "Clinical Trial Not Allowed," which means the funded work must be non-clinical in the NIH sense: applicants should not propose prospective human intervention studies designed to evaluate health-related biomedical outcomes. Instead, the emphasis is on laboratory-based and preclinical research, including work with derived human cells and tissues, model systems, and analyses that do not meet NIH’s definition of a clinical trial.

In terms of funding details, the opportunity is categorized as a discretionary grant in the health and education activity area, listed under CFDA number 93.279, and is administered by NIH. The posted award ceiling is $500,000. The original closing date listed for applications was 2019-11-12, and the FOA creation date was 2019-07-10, which signals that this is a time-bound solicitation from that period; anyone interested would need to confirm current availability or related reissued opportunities through NIH.

Eligibility is broad across U.S.-based organizations and includes many categories commonly allowed under NIH research programs. Eligible applicants include state, county, city/township, and special district governments; independent school districts; public and state-controlled institutions of higher education; private institutions of higher education; nonprofits (both with and without 501(c)(3) status, excluding higher education institutions in those nonprofit categories); public housing authorities/Indian housing authorities; for-profit organizations (other than small businesses); small businesses; and certain tribal entities, including federally recognized tribal governments and tribal organizations other than federally recognized governments. The FOA also highlights additional eligible applicant types 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.

At the same time, the FOA places clear restrictions on foreign involvement. Non-domestic (non-U.S.) entities and non-domestic components of U.S. organizations are not eligible to apply, and foreign components, as defined in the NIH Grants Policy Statement, are not allowed. In practical terms, this means the applicant organization must be domestic, and the proposed work cannot rely on foreign subawards or foreign components as part of the funded project structure under NIH’s definitions.

Overall, this FOA is aimed at advancing the field’s ability to model and explain HAND in the cART era by using human iPSC-derived microglia and cerebral organoids as experimentally tractable, disease-relevant platforms. The intended outcome is deeper insight into the biological mechanisms that sustain HIV-related neurological complications despite effective systemic treatment, potentially laying groundwork for future therapeutic targets or strategies to prevent or mitigate persistent neurocognitive and neuropathological effects in people living with HIV.

• The National Institutes of Health in the education, health sector is offering a public funding opportunity titled "Modeling HIV Neuropathology Using Microglia from Human iPSC and Cerebral Organoids (R01 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 2019-07-10.
• Applicants must submit their applications by 2019-11-12. (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 20 023

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