Silencing of HIV-1 Proviruses (R61/R33) | Apply Online

FAQs: The Silencing of HIV-1 Proviruses (R61/R33) - RFA-AI-16-038

What is this funding opportunity?

This is an NIH funding opportunity titled "The Silencing of HIV-1 Proviruses (R61/R33)" (RFA-AI-16-038), issued by the U.S. Department of Health and Human Services, National Institutes of Health (NIH). It supports research aimed at shutting down HIV-1 proviruses through epigenetic mechanisms.

What is the main scientific goal of the FOA?

The goal is to advance strategies that drive long-term, potentially permanent silencing of integrated HIV-1 DNA (proviruses) by engaging the host cell's epigenetic machinery, rather than directly targeting viral proteins.

What types of therapeutic candidates does the FOA prioritize?

The FOA emphasizes discovery and refinement of therapeutic candidates such as small molecules or RNA-based agents that can interface with host-controlled chromatin and transcriptional regulation to keep HIV proviruses locked in an inactive state.

Does this opportunity focus on targeting HIV viral proteins?

No. The emphasis is on manipulating host epigenetic and transcriptional regulation so that proviruses remain transcriptionally silent, rather than directly inhibiting viral proteins.

What is meant by epigenetic silencing in the context of this FOA?

Epigenetic silencing here refers to host-driven control of gene expression affecting HIV proviruses, including changes to histone modifications, DNA methylation patterns, chromatin accessibility, or recruitment of transcriptional repressors, with the intent of establishing a stable "off" state for the virus.

Why is proviral silencing considered important for HIV remission or cure strategies?

HIV can persist because proviral DNA integrates into the host genome and may remain silent in reservoirs, with the potential to reactivate later. This FOA supports approaches that reinforce or induce silencing to reduce the chance of reactivation and support durable remission or functional cure concepts.

Is this FOA aligned with the "block-and-lock" approach?

Yes. The opportunity targets a strategy often described as "block-and-lock," which aims to push HIV into deep, durable, epigenetically enforced latency.

What grant mechanism does this FOA use?

This program uses a bi-phasic Exploratory and Developmental structure (R61/R33), supporting two linked stages of work: an initial exploratory phase followed by a development/optimization phase.

What is the purpose of the R61 phase?

The R61 phase generally supports early proof-of-concept activities such as identifying promising small molecules or RNA candidates, demonstrating influence on relevant epigenetic pathways, and generating initial evidence of proviral suppression in appropriate models.

What is the purpose of the R33 phase?

The R33 phase is intended for more advanced development and optimization, which may include improving potency and specificity, validating durable silencing, refining delivery approaches for RNA-based strategies, expanding testing into more rigorous biological systems, and strengthening the preclinical package.

Do applicants need to compete for a separate mechanism between the two phases?

The FOA is designed to help projects move from discovery into a more mature development track without competing for an entirely separate mechanism in between, assuming transition criteria are met.

What kinds of research activities does the FOA explicitly call for?

The announcement explicitly calls for identification and optimization efforts, signaling interest in projects that go beyond basic observations to systematically improve candidate agents toward a more translationally relevant form.

Who is eligible to apply?

Eligibility is broad and includes: state, county, and local governments; 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 tribal organizations; public housing authorities/Indian housing authorities; nonprofit organizations with or without 501(c)(3) status (outside of higher education institutions); for-profit organizations (other than small businesses); small businesses; and other applicants as allowed under the FOA's additional eligibility language.

Does NIH appear to be encouraging both academic and industry applicants?

Yes. The wide eligibility scope suggests NIH intended to attract applications from academia, nonprofit research institutes, government-affiliated research entities, and industry, including small biotech companies capable of developing small-molecule or RNA therapeutic leads.

What agency issued and administers this opportunity?

This opportunity was issued by the U.S. Department of Health and Human Services, National Institutes of Health (NIH).

What is the opportunity number or identifier?

The funding opportunity announcement (FOA) is identified as RFA-AI-16-038.

When was the FOA created and posted?

The FOA was created and posted on May 26, 2016.

What was the closing date for applications?

The original and current closing date listed is December 7, 2016.

What is the maximum award amount mentioned in the listing?

The listed award ceiling is $500,000, indicating an upper bound on the amount of funding expected per award under the announcement.

How many awards does NIH expect to make under this FOA?

The number of expected awards is not specified in the provided listing. In some cases this is left unspecified because funding depends on application volume, scientific merit, and available appropriations.

What type of funding opportunity is this described as?

It is described as a discretionary grant opportunity in the NIH health and education-related research space.

Which CFDA numbers are associated with this FOA?

The opportunity is associated with CFDA numbers 93.242, 93.279, 93.855, 93.856.

Is this FOA more basic science or translational development?

Based on the description provided, it supports a pipeline that begins with exploratory proof-of-concept work and moves into development and optimization of candidate agents, indicating a strong translational development emphasis alongside mechanistic epigenetic goals.

What is the central approach to achieving durable silencing, according to the FOA summary?

The central approach is to identify and optimize agents that engage host epigenetic regulators to alter chromatin and transcriptional control in ways that keep HIV proviruses stably inactive over the long term.