Advances in Precision Editing Therapies for Alpha-1 Antitrypsin Deficiency

Jenny Gao; Erik Sontheimer; Terence R Flotte; Wen Xue

doi:10.1177/10430342261417356

Advances in Precision Editing Therapies for Alpha-1 Antitrypsin Deficiency

Hum Gene Ther. 2026 Jan 26:10430342261417356. doi: 10.1177/10430342261417356. Online ahead of print.

Authors

Jenny Gao¹, Erik Sontheimer^{1

2

3

4}, Terence R Flotte^{3

5

6}, Wen Xue^{1

2

3

7}

Affiliations

¹ RNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, Massachusetts, USA.
² Department of Molecular Medicine, University of Massachusetts Chan Medical School, Worcester, Massachusetts, USA.
³ Li Weibo Institute for Rare Diseases Research, University of Massachusetts Chan Medical School, Worcester, Massachusetts, USA.
⁴ Department of Biochemistry and Molecular Biotechnology, University of Massachusetts Chan Medical School, Worcester, Massachusetts, USA.
⁵ Horae Gene Therapy Center, University of Massachusetts Chan Medical School, Worcester, Massachusetts, USA.
⁶ Department of Pediatrics, University of Massachusetts Chan Medical School, Worcester, Massachusetts, USA.
⁷ Department of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, Massachusetts, USA.

PMID: 41588875
DOI: 10.1177/10430342261417356

Abstract

Genome and RNA editing modalities have revolutionized precision gene therapy, offering a safer alternative to traditional gene replacement approaches. Alpha-1 antitrypsin deficiency (AATD) is a compelling model for precision medicine because the disease mechanism is well defined-mutations in a single gene are responsible for both liver and lung pathology. In this review, we summarize the current preclinical and clinical efforts for AATD, with an emphasis on genome and RNA editing strategies.

Keywords: RNA editing; alpha-1 antitrypsin; base editing; gene editing; prime editing.

Publication types

Review