# Development of AAV vectors for CF therapy

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2021 · $388,750

## Abstract

Abstract
Cystic fibrosis (CF) is caused by mutations of the CF transmembrane conductance regulator (CFTR) gene.
Airway disease is the leading cause of morbidity and mortality. Gene therapy offers a potential cure for CF.
Among gene delivery vehicles, adeno-associated virus (AAV) vectors have demonstrated success in clinical
trials. AAV vectors have also been tested in CF patients via airway delivery for gene addition but without
measurable success perhaps due to physical airway barriers and inefficient transduction. Studies have shown
that higher AAV transduction of airway epithelial cells occur via the basolateral membrane in vitro and our
preliminary study demonstrated that systemic administration of AAV vectors induced much more efficient lung
transduction than airway delivery in mice. These findings strongly suggest that AAV can transduce airway
epithelial cells via systemic administration. The efficiency of AAV transduction in airway epithelial cells after
systemic delivery of AAV vectors is usually restricted by the blood vascular barrier and a high prevalence of
AAV neutralizing antibodies (Nabs). In this proposal, based on our previous studies, we will explore different
strategies to develop novel AAV vectors using directed evolution and AAV virion specific binding peptides via
phage display technology to increase AAV vector vascular permeability for enhanced transduction in airway
epithelial cells and to evade Nabs after systemic administration. Finally, the novel approaches developed in
this proposal will be used to deliver optimized CRISPR/Cas9 specific for CFTR del508 to CF mice and study
the long-term phenotypic correction. The results generated from these studies will allow us to develop an
effective approach to treat CF patients using AAV vector mediated gene delivery.
.

## Key facts

- **NIH application ID:** 10117463
- **Project number:** 1R01HL151348-01A1
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Chengwen Li
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $388,750
- **Award type:** 1
- **Project period:** 2020-12-15 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10117463

## Citation

> US National Institutes of Health, RePORTER application 10117463, Development of AAV vectors for CF therapy (1R01HL151348-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10117463. Licensed CC0.

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