Current clinical applications of AAV-mediated gene therapy.
Journal
Molecular therapy : the journal of the American Society of Gene Therapy
Journal Volume
33
Journal Issue
6
Start Page
2479
End Page
2516
ISSN
1525-0024
Date Issued
2025-06-04
Author(s)
Byrne, Barry J
Flanigan, Kevin M
Matesanz, Susan E
Finkel, Richard S
Waldrop, Megan A
D'Ambrosio, Eleonora S
Johnson, Nicholas E
Smith, Barbara K
Bönnemann, Carsten
Carrig, Sean
Rossano, Joseph W
Greenberg, Barry
Lalaguna, Laura
Lara-Pezzi, Enrique
Subramony, Sub
Corti, Manuela
Mercado-Rodriguez, Claudia
Leon-Astudillo, Carmen
Ahrens-Nicklas, Rebecca
Bharucha-Goebel, Diana
Gao, Guangping
Gessler, Dominic J
Boye, Sanford L
Boye, Shannon E
George, Lindsey A
Abstract
Currently, there are an estimated 8,000 genetic disorders that cumulatively affect approximately 10% of the population. Even among the 5% of patients with genetic disease that have treatment options, these therapeutics rarely address the underlying cause of disease but rather focus on managing or modifying symptoms and typically require recurrent, lifelong therapy. A therapeutic approach to genetic disease that in vivo delivers a functional copy of the aberrant gene is an intuitive solution that has thus far taken 3 decades to reduce to clinical practice, predominantly using adeno-associated viral (AAV) vectors. Among available viral and non-viral gene delivery approaches, AAV vectors remain the most efficient means for in vivo delivery of DNA to the nucleus. AAV vectors now constitute a bone fide novel therapeutic drug class composed of seven US Food and Drug Administration-approved products with over 10-fold more in clinical development for an expanding number of disease indications and an identified list of problems to overcome for widespread clinical application. Here, we review current progress in clinical AAV gene therapy, including for neuromuscular disorders, hemophilia, primary cardiovascular disorders, or disorders with cardiovascular manifestations, lysosomal storage disorders, mucopolysaccharide disorders, primary central nervous systemic disorders, and ocular disorders.
Subjects
adeno-associated viral vectors
in vivo gene therapy
SDGs
Type
journal article