# Impact of ATP-binding cassette A3 (ABCA3) mutations on alveolar type 2 cell function and genetic complementation

> **NIH NIH R03** · UNIVERSITY OF IOWA · 2024 · $173,175

## Abstract

Summary/Abstract
Pulmonary surfactant is comprised of phospholipids and protein components and helps prevent
lung collapse by lowering surface tension in alveolar lining fluid. ATP-binding cassette A3
(ABCA3) is a cyclic AMP-activated phospholipid transporter that localizes to the limiting
membrane of lamellar bodies in alveolar type 2 epithelial cells (AEC2s). Genetic variants in
ABCA3 can cause severe neonatal respiratory distress syndrome (RDS) or later onset
pulmonary fibrosis and are the most common genetic causes of childhood interstitial lung
diseases (chILD). Other than lung transplant, there are no specific treatments for severe cases
of ABCA3 deficiency. Since ABCA3 deficiency is autosomal recessive, it should be amenable to
gene addition strategies. Complementing the loss of function with a full length ABCA3 cDNA
reverses surfactant deficiency phenotypes in vitro. Our overall goals are to 1) understand the
biological effects of ABCA3 mutations in human AEC2s and 2) actualize a gene therapy
strategy to modify the disease course by efficiently and persistently expressing ABCA3 at
physiological levels in AEC2s.

## Key facts

- **NIH application ID:** 10953882
- **Project number:** 1R03TR004814-01A1
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** PAUL B MCCRAY
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $173,175
- **Award type:** 1
- **Project period:** 2024-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10953882

## Citation

> US National Institutes of Health, RePORTER application 10953882, Impact of ATP-binding cassette A3 (ABCA3) mutations on alveolar type 2 cell function and genetic complementation (1R03TR004814-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10953882. Licensed CC0.

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