Opportunity Information: Apply for RFA AI 17 013
The National Institutes of Health (NIH) grant opportunity titled "Silencing of HIV-1 Proviruses (R61/R33)" (Funding Opportunity Number RFA AI 17 013) supports early-stage, high-potential research aimed at a long-standing challenge in HIV treatment: the persistence of HIV in a latent, integrated form (the provirus) inside host cells. Even when antiretroviral therapy suppresses active viral replication, proviruses can remain hidden and capable of reactivating, which is a major barrier to curing HIV. This FOA focuses on a "block-and-lock" style strategy, meaning it is interested in approaches that drive HIV into a deep, durable state of transcriptional silence rather than trying to shock it out of latency.
The scientific goal of the program is to fund exploratory and developmental projects that identify and optimize either small molecules or RNA-based agents that can engage the host cell's epigenetic machinery to produce long-term or potentially permanent epigenetic silencing of HIV-1 proviruses. In practical terms, this means applicants are expected to look for interventions that modify or recruit host factors involved in chromatin regulation (for example, pathways that control histone modifications, DNA methylation, chromatin remodeling, or other transcriptional control systems) in a way that keeps HIV proviral DNA locked down and unable to restart active infection. The emphasis on host epigenetic machinery reflects an interest in targeting cellular systems that regulate proviral transcriptional competence, potentially making silencing more stable than approaches that act only on viral proteins.
The mechanism is bi-phasic (R61/R33), which is designed to support a progression from initial, milestone-driven exploration into a more advanced development phase if the early aims succeed. The first phase (R61) is generally used for proof-of-concept and feasibility work, such as discovering candidate compounds or RNAs, developing or validating assays, demonstrating target engagement, showing early evidence of proviral silencing, and establishing initial structure-activity relationships or optimization parameters. The second phase (R33) is intended for projects that meet the R61 milestones and are ready to move into more robust optimization and development activities, such as improving potency and selectivity, refining delivery strategies for RNA-based approaches, expanding validation across relevant cell models, and generating deeper evidence that silencing is durable and mechanistically tied to epigenetic regulation. The overall structure is meant to reduce risk for promising but still-developing ideas by creating a clear gateway between exploratory work and more resource-intensive development.
From an administrative perspective, this is a discretionary grant program under NIH, with activity categories spanning education and health, and CFDA numbers listed as 93.242, 93.279, 93.855, and 93.856. The opportunity was created on 2017-05-17, and the original closing date was 2017-12-06. The listed award ceiling is $500,000. While the number of expected awards is not specified in the provided source data, the budget cap gives a sense of the scale NIH envisioned for individual projects under this announcement.
Eligibility is broad and includes many types of U.S. organizations and governmental units, reflecting NIH's aim to attract a wide range of scientific and translational expertise. Eligible applicants include state, county, and city or township governments; special district governments; independent school districts; public and state-controlled institutions of higher education; private institutions of higher education; Native American tribal governments (federally recognized) and Native American tribal organizations (other than federally recognized tribal governments); public housing authorities and Indian housing authorities; nonprofits with and without 501(c)(3) status (excluding institutions of higher education in those nonprofit categories as listed); for-profit organizations other than small businesses; and small businesses, along with other applicants as allowed. In addition, the FOA explicitly highlights other eligible applicant categories such as Alaska Native and Native Hawaiian Serving Institutions; Asian American Native American Pacific Islander Serving Institutions (AANAPISIs); Historically Black Colleges and Universities (HBCUs); Hispanic-serving Institutions; Tribally Controlled Colleges and Universities (TCCUs); faith-based or community-based organizations; eligible federal agencies; regional organizations; U.S. territories or possessions; Indian/Native American tribal governments other than federally recognized entities; and non-domestic (non-U.S.) entities, meaning foreign organizations can also apply.
Overall, the opportunity is best understood as NIH support for pipeline-style research that starts with discovery and moves toward optimization of agents that can enforce durable epigenetic repression of HIV proviruses. It is geared toward applicants who can connect mechanistic epigenetics with rigorous HIV latency models and can propose clear milestones demonstrating that their candidate small molecule or RNA not only reduces proviral transcription, but does so through definable interactions with host epigenetic systems in a way that could plausibly remain stable over time.Apply for RFA AI 17 013
- The National Institutes of Health in the education, health sector is offering a public funding opportunity titled "Silencing of HIV-1 Proviruses (R61/R33)" and is now available to receive applicants.
- Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.242, 93.279, 93.855, 93.856.
- This funding opportunity was created on 2017-05-17.
- Applicants must submit their applications by 2017-12-06. (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.
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FAQs: NIH "Silencing of HIV-1 Proviruses (R61/R33)" (RFA AI 17 013)
What is the title of this NIH funding opportunity?
The opportunity is titled "Silencing of HIV-1 Proviruses (R61/R33)."
What is the Funding Opportunity Number (FOA number)?
The Funding Opportunity Number provided is RFA AI 17 013.
What problem in HIV treatment is this FOA trying to address?
This FOA targets a major barrier to curing HIV: the persistence of HIV in a latent, integrated form (the provirus) inside host cells. Even when antiretroviral therapy suppresses active viral replication, proviruses can remain hidden and capable of reactivating.
What overall strategy does this FOA prioritize?
The FOA emphasizes a "block-and-lock" style strategy. That means it is interested in approaches that drive HIV into a deep, durable state of transcriptional silence, rather than attempting to reactivate ("shock") latent virus.
What is the scientific goal of the program?
The program aims to fund exploratory and developmental projects that identify and optimize either small molecules or RNA-based agents that can engage the host cell's epigenetic machinery to produce long-term or potentially permanent epigenetic silencing of HIV-1 proviruses.
What types of therapeutic or research agents are of interest?
Applicants are expected to identify and optimize either (1) small molecules or (2) RNA-based agents designed to induce durable epigenetic silencing of HIV-1 proviruses through interactions with host epigenetic machinery.
What does it mean to "engage the host cell's epigenetic machinery" in this context?
In practical terms, it means interventions that modify or recruit host factors involved in chromatin regulation so that HIV proviral DNA remains locked down and unable to restart active infection. Examples mentioned include pathways controlling histone modifications, DNA methylation, chromatin remodeling, or other transcriptional control systems.
Why does the FOA emphasize targeting host epigenetic systems instead of only viral targets?
The FOA highlights host epigenetic machinery because cellular systems regulate proviral transcriptional competence. Targeting these host regulatory systems may make silencing more stable than approaches acting only on viral proteins.
What grant mechanism is being used?
The mechanism is bi-phasic: R61/R33.
How does the two-phase (R61/R33) structure work at a high level?
The structure supports progression from an initial, milestone-driven exploration phase (R61) into a more advanced development phase (R33) if early aims succeed. It is designed to reduce risk for promising but still-developing ideas by creating a clear gateway between exploratory work and more resource-intensive development.
What kinds of activities are typically appropriate for the R61 phase?
The R61 phase is generally used for proof-of-concept and feasibility work such as discovering candidate compounds or RNAs, developing or validating assays, demonstrating target engagement, showing early evidence of proviral silencing, and establishing initial structure-activity relationships or optimization parameters.
What kinds of activities are typically appropriate for the R33 phase?
The R33 phase is intended for projects that meet the R61 milestones and are ready for more robust optimization and development activities. Examples include improving potency and selectivity, refining delivery strategies for RNA-based approaches, expanding validation across relevant cell models, and generating deeper evidence that silencing is durable and mechanistically tied to epigenetic regulation.
What is meant by "milestone-driven" in this FOA?
The FOA is described as milestone-driven because advancement from the exploratory R61 phase to the development-focused R33 phase is intended to occur only if the R61 milestones are met, creating a defined decision point between phases.
What types of evidence does the FOA suggest applicants should ultimately generate?
The FOA describes an emphasis on showing that a candidate small molecule or RNA reduces proviral transcription and does so through definable interactions with host epigenetic systems, with evidence suggesting the silencing could remain stable over time.
Is this FOA focused on discovery, development, or both?
Both. It supports a pipeline-style progression starting with discovery and feasibility work (R61) and moving toward optimization and development (R33) for approaches that can enforce durable epigenetic repression of HIV proviruses.
What is the award ceiling listed for this opportunity?
The listed award ceiling is $500,000.
Is the number of expected awards provided?
No. The provided information notes that the number of expected awards is not specified in the source data.
When was this opportunity created and when did it close?
The opportunity was created on 2017-05-17, and the original closing date was 2017-12-06.
Which agency is offering this funding opportunity?
The funding opportunity is offered by the National Institutes of Health (NIH).
What program type is this from an administrative perspective?
It is described as a discretionary grant program under NIH.
What activity categories are associated with this opportunity?
The activity categories are listed as spanning education and health.
What CFDA numbers are associated with this opportunity?
The CFDA numbers listed are 93.242, 93.279, 93.855, and 93.856.
Who is eligible to apply?
Eligibility is broad and includes many types of U.S. organizations and governmental units, as well as other applicant categories specifically highlighted in the FOA information provided.
Are state, local, or tribal governments eligible?
Yes. Eligible applicants include state governments, county governments, city or township governments, special district governments, and Native American tribal governments (federally recognized). The eligibility list also includes Indian/Native American tribal governments other than federally recognized entities and Native American tribal organizations (other than federally recognized tribal governments).
Are higher education institutions eligible?
Yes. Eligible applicants include public and state-controlled institutions of higher education and private institutions of higher education. The FOA also highlights serving institutions such as HBCUs, Hispanic-serving Institutions, TCCUs, Alaska Native and Native Hawaiian Serving Institutions, and AANAPISIs.
Are nonprofits eligible?
Yes. Eligible applicants include nonprofits with 501(c)(3) status (other than institutions of higher education) and nonprofits without 501(c)(3) status (other than institutions of higher education), as listed in the provided information.
Are for-profit organizations eligible?
Yes. Eligible applicants include for-profit organizations other than small businesses, and small businesses.
Can foreign (non-U.S.) organizations apply?
Yes. The FOA information provided states that non-domestic (non-U.S.) entities are eligible, meaning foreign organizations can also apply.
Are U.S. territories or possessions eligible to apply?
Yes. The FOA explicitly highlights U.S. territories or possessions as an eligible applicant category.
Does the FOA mention eligibility for faith-based or community-based organizations?
Yes. Faith-based or community-based organizations are explicitly highlighted among eligible applicant categories.
Are public housing authorities eligible?
Yes. Public housing authorities and Indian housing authorities are included in the eligibility list.
Are federal agencies eligible applicants?
Yes. The FOA highlights eligible federal agencies as an eligible applicant category.
What kinds of research teams or capabilities seem most aligned with the FOA's aims?
Based on the description provided, the opportunity is geared toward applicants who can connect mechanistic epigenetics with rigorous HIV latency models and propose clear milestones. The work is expected to tie proviral transcriptional silencing to host epigenetic regulation and to support an optimization pipeline for small molecules or RNA-based agents.
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