# Directed Evolution of Novel AAV Capsis for Global CNS Delivery in Rodents and Primates

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2020 · $570,525

## Abstract

TITLE: Directed Evolution of Novel AAV Capsids for Global CNS Delivery in Rodents and
Primates
ABSTRACT
Many monogenic based neurological disorders present attractive targets for gene therapy, but
even with promising proof-of-concept rodent studies, successful clinical translation depends
upon efficient transgene delivery and expression across the entire central nervous system
(CNS). Directed evolution is a powerful and proven method to develop novel adeno-associated
virus (AAV) vector capsids that exhibit properties distinct from naturally occurring serotypes.
However, to date, the majority of novel capsids have been derived in rodents or in vitro models
whose properties may or may not translate to other species, in particular primates. This
proposal will utilize AAV capsid DNA shuffling directed evolution to develop gene delivery
vectors for a number of human CNS disease applications. To do this, parallel selections and
recovered clone characterization will be carried out in mice and non-human primates (NHPs),
combining the expertise of experts on both CNS gene transfer in NHPs and AAV vector design.
The experimental plan should independently generate superior AAV capsids capable of global
CNS delivery, with cross-compatibility between mice and NHPs. Moreover, we have designed
our experimental approach to generate vectors that exhibit selective tropism for neurons,
astrocytes, and/or oligodendrocytes, which would be invaluable reagents for research and
therapeutic applications. If successful, the AAV capsid reagents generated should create new
research tools, broaden the application of gene therapy to more CNS disorders, and facilitate
the translation of existing CNS gene therapy approaches to humans.

## Key facts

- **NIH application ID:** 9790984
- **Project number:** 5R01NS095867-04
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Steven J Gray
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $570,525
- **Award type:** 5
- **Project period:** 2016-09-30 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9790984

## Citation

> US National Institutes of Health, RePORTER application 9790984, Directed Evolution of Novel AAV Capsis for Global CNS Delivery in Rodents and Primates (5R01NS095867-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9790984. Licensed CC0.

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