# Novel AAV Capsids and Gene Regulatory Elements for GeneExpression in Microglia

> **NIH NIH R21** · BROAD INSTITUTE, INC. · 2022 · $200,000

## Abstract

Project Summary:
Microglia, the resident macrophages of the brain, assume a multitude of functions during brain development and
disease. Long known to react to changes in brains affected by Alzheimer’s disease (AD), genetic studies of late-
onset AD indicate that AD risk variants are commonly found in or near genes that are specifically expressed in
microglia, suggesting that microglia play an active role in driving AD. In addition, microglia exhibit various
functions during brain development, including synapse pruning. Genes coding for components of the
complement system, which mediates synapse pruning by microglia, have been linked to schizophrenia.
However, a major bottleneck in studying the roles of microglia in normal and diseased brains is the lack of viral
tools for rapidly manipulating their gene expression. Viral vectors would also benefit studies where transgenic
animals are not available. Finally, viral vectors would enable studies on the potential of gene therapy for AD and
rare diseases that affect microglia. However, while microglia show modest and localized transduction by
lentiviruses in vivo, they are resistant to transduction by adeno-associated viruses (AAVs), the preferred viral
vectors used in neuroscience research and gene therapy due to their superior spread and excellent safety profile.
Here we propose to elucidate the barriers to microglia transduction by AAVs, engineer AAV capsid variants that
are able to overcome these barriers and transduce microglia in vivo, and develop novel gene regulatory elements
that will enable microglia-specific transgene expression from viral vectors. This will be a collaborative project
between the Stevens and Deverman labs, combining their expertise in studying microglia (Stevens) and in
developing novel AAV vectors (Deverman).

## Key facts

- **NIH application ID:** 10376863
- **Project number:** 5R21MH126409-02
- **Recipient organization:** BROAD INSTITUTE, INC.
- **Principal Investigator:** Benjamin E Deverman
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $200,000
- **Award type:** 5
- **Project period:** 2021-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10376863

## Citation

> US National Institutes of Health, RePORTER application 10376863, Novel AAV Capsids and Gene Regulatory Elements for GeneExpression in Microglia (5R21MH126409-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10376863. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*