# Dose control of recombinant Adeno-associated virus with Chemical Epigenetic Modifiers

> **NIH NIH F31** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2024 · $36,435

## Abstract

Abstract
 Recombinant adeno-associated virus (rAAV) is a non-replicative DNA viral vector that is
used in three FDA approved gene therapies and many ongoing clinical trials. Despite the
popularity of rAAV as a therapeutic vehicle, there exists no generalizable method of tightly
controlling rAAV transgene dose. After transduction, most rAAV genomes persist as concatemeric
episomes that are retained over time in non-proliferating cells. Recent evidence suggests that
rAAV episomes are chromatinized and epigenetically regulated, although further inquiry is needed
to clarify the relationship between epigenetic modifications and rAAV transgene expression. The
Hathaway Laboratory has developed a novel, titratable, and reversible system of epigenetic
editing that uses bifunctional small molecules, called Chemical Epigenetic Modifiers (CEMs), to
recruit endogenous epigenetic machinery to targeted genetic loci. We hypothesize that potent
and specific next-generation CEM compounds (SLF* CEMs) could be applied to chemically
regulate rAAV transgene expression. In Aim 1, SLF* CEM-based systems of rAAV regulation will
be constructed and screened for efficacy in human cell lines. In Aim 2, the putative epigenetic
mechanism of CEM-mediated rAAV regulation will be interrogated through knock
down/replacement and CUT&RUN-Sequencing experiments. The results of this study could
provide a foundation for the development of a system of epigenetically tuning the dose of rAAV-
based gene therapies without the need for vector readministration.

## Key facts

- **NIH application ID:** 10901141
- **Project number:** 1F31AI179044-01A1
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Sara Rose Wasserman
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $36,435
- **Award type:** 1
- **Project period:** 2024-08-12 → 2025-06-22

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10901141

## Citation

> US National Institutes of Health, RePORTER application 10901141, Dose control of recombinant Adeno-associated virus with Chemical Epigenetic Modifiers (1F31AI179044-01A1). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10901141. Licensed CC0.

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