# RE-ENGINEERING AAV GENOME PACKAGING

> **NIH NIH R01** · DUKE UNIVERSITY · 2021 · $486,413

## Abstract

ABSTRACT
 Recombinant adeno-associated viruses (AAV) are promising vectors for human gene therapy. Despite
regulatory approval and a rapidly growing pipeline, clinical data have indicated that vector dose-related
hepatotoxicity is a significant concern. Recent preclinical studies suggest that heterogeneity in AAV vector
preparations, including the presence of defective interfering particles with partial or truncated genomes
contribute to such undesirable side effects. Although somewhat resolvable with anti-inflammatory drug
regimens, permanent loss of gene expression has been reported. We postulate that improvements to AAV
vector design and composition are likely to improve the safety profile. To achieve the latter goals, a better
understanding of particle heterogeneity in AAV vectors packaging different genomes as well as the impact of
such on AAV biology is essential. In the current proposal, we will first advance a potentially disruptive
technology, charge detection mass spectrometry (CDMS) to help map the mass landscape of vector
compositions associated with genome packaging. We will then bridge this basic information with new directions
in AAV capsid engineering with the goal of improving compositional homogeneity and reducing the potential for
side effects. Each aim is tailored to directly interrogate the proposed correlation between the composition of
recombinant vectors with viral infectivity in cell culture as well as gene transfer efficiency and toxicity in mouse
models. We expect our efforts to (i) offer significant, new insight into parvoviral capsid-genome interactions, (ii)
enable the development and validation of a novel analytical technique for rapid screening and quality testing of
clinical AAV samples, and (iii) improve AAV gene transfer efficiency and safety profile through capsid
engineering.

## Key facts

- **NIH application ID:** 10141259
- **Project number:** 5R01GM127708-05
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Aravind Asokan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $486,413
- **Award type:** 5
- **Project period:** 2018-05-15 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10141259

## Citation

> US National Institutes of Health, RePORTER application 10141259, RE-ENGINEERING AAV GENOME PACKAGING (5R01GM127708-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10141259. Licensed CC0.

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