# Clinical Trial and Immunologic aspects of muscle-directed rAAV1-AAT gene therapy

> **NIH NIH P01** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2020 · $502,500

## Abstract

Abstract
Deficiency of alpha-1 antitrypsin (AAT) is a relatively common genetic disorder, which leads to emphysema in
the majority of symptomatic patients. While AAT is normally produced in the liver, and to a lesser extent in
monocytes and macrophages, our laboratory has developed a clinical rAAV1-hAAT vector which mediates
long-term, ectopic supplementation from muscle, thus avoiding potential for liver toxicity, which may be more
likely in the AAT-deficient liver. The current vector has progressed through IM phase 1 and phase 2a trials
which have shown dose-related expression persisting for years after 1 IM injection and the presence of
regulatory T cells (Tregs) specific for AAV capsid. In the current application, we propose to complete preclinical
studies necessary to move to the phase 2b trial, to complete that trial and to develop a method to study and
control the Treg response, using novel humanized mouse models. The project is highly interactive with each of
the cores and with projects 2, 3 and 4.

## Key facts

- **NIH application ID:** 9935131
- **Project number:** 5P01HL131471-05
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** Terence R. Flotte
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $502,500
- **Award type:** 5
- **Project period:** — → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9935131

## Citation

> US National Institutes of Health, RePORTER application 9935131, Clinical Trial and Immunologic aspects of muscle-directed rAAV1-AAT gene therapy (5P01HL131471-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9935131. Licensed CC0.

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