Related Experiment Video
Updated: Jun 27, 2025
Production of Adeno-Associated Virus Vectors in Cell Stacks for Preclinical Studies in Large Animal Models
Published on: June 30, 2021
Comparative in vivo characterization of newly discovered myotropic adeno-associated vectors
Jacqueline Ji1, Elise Lefebvre1, Jocelyn Laporte2
1Institute of Genetics and Molecular and Cellular Biology (IGBMC), INSERM U1258, CNRS UMR7104, University of Strasbourg, IGBMC, 1 rue Laurent Fries, Illkirch, 67404, France.
Background:
Adeno-associated virus (AAV)-based gene therapy is a promising strategy to treat muscle diseases. However, this strategy is currently confronted with challenges, including a lack of transduction efficiency across the entire muscular system and toxicity resulting from off-target tissue effects. Recently, novel myotropic AAVs named MyoAAVs and AAVMYOs have been discovered using a directed evolution approach, all separately demonstrating enhanced muscle transduction efficiency and liver de-targeting effects. However, these newly discovered AAV variants have not yet been compared.
Methods:
In this study, we performed a comparative analysis of these various AAV9-derived vectors under the same experimental conditions following different injection time points in two distinct mouse strains.
Results:
We highlight differences in transduction efficiency between AAV9, AAVMYO, MyoAAV2A and MyoAAV4A that depend on age at injection, doses and mouse genetic background. In addition, specific AAV serotypes appeared more potent to transduce skeletal muscles including diaphragm and/or to de-target heart or liver.
Conclusions:
Our study provides guidance for researchers aiming to establish proof-of-concept approaches for preventive or curative perspectives in mouse models, to ultimately lead to future clinical trials for muscle disorders.
