# Evolving High Potency AAV Vectors for Neuromuscular Genome Editing

> **NIH NIH UG3** · DUKE UNIVERSITY · 2020 · $663,989

## Abstract

ABSTRACT
Recombinant adeno-associated viruses (AAV) have emerged as safe and effective vectors for clinical gene
therapy applications including systemic treatment of neuromuscular diseases such as Spinal Muscular Atrophy
(SMA), Duchenne Muscular Dystrophy (DMD), and Giant Axonal Neuropathy (GAN) amongst others. However,
enabling gene editing therapeutics to treat human disease requires improved systems that achieve effective
genome editing at low systemic AAV vector doses in multiple animal models. Additionally, the ideal target cell
types for gene editing, including progenitor cells, are distinct from the target cells that conventional gene delivery
vectors have been optimized for. Genome editing in neuromuscular tissue, in particular, is challenging. To date,
no effective non-viral delivery vehicles have been identified for widespread genome editing in musculoskeletal
and neurological tissue following systemic administration. Further, in case of AAV vectors, several challenges
pertinent to delivery of genome editors remain. The rationale for our current proposal stems from barriers posed
by (i) species-related differences observed in AAV tropism, (ii) presence of pre-existing neutralizing antibodies
to natural AAV, (iii) the need for high systemic AAV doses to achieve neuromuscular gene transfer, (iv) vector
dose-related toxicity as indicated by detection of liver transaminases in patients, and (v) the unique opportunity
to correct progenitor cells in situ. To address these aspects, we have assembled a collaborative team with cross-
cutting expertise and developed a comprehensive and innovative approach to evolve high potency AAV variants
for systemic neuromuscular genome editing. Specifically, we will focus our efforts on evolving high potency AAV
vectors for neuromuscular genome editing using a three-tiered approach applied across different species, tissues
and cell types.

## Key facts

- **NIH application ID:** 9997665
- **Project number:** 5UG3AR075336-03
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Aravind Asokan
- **Activity code:** UG3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $663,989
- **Award type:** 5
- **Project period:** 2018-09-10 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9997665

## Citation

> US National Institutes of Health, RePORTER application 9997665, Evolving High Potency AAV Vectors for Neuromuscular Genome Editing (5UG3AR075336-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9997665. Licensed CC0.

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