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Differential myofiber-type transduction preference of adeno-associated virus serotypes 6 and 9

Authors :
Riaz, Muhammad
Raz, Yotam
Moloney, E.
van Putten, Maaike
Krom, Yvonne D
van der Maarel, Silvere M
Verhaagen, J.
Raz, Vered
Riaz, Muhammad
Raz, Yotam
Moloney, E.
van Putten, Maaike
Krom, Yvonne D
van der Maarel, Silvere M
Verhaagen, J.
Raz, Vered
Source :
Skeletal Muscle vol.5 (2015) p.37 [ISSN 2044-5040]
Publication Year :
2015

Abstract

BACKGROUND: Gene therapy strategies are promising therapeutic options for monogenic muscular dystrophies, with several currently underways. The adeno-associated viral (AAV) vector is among the most effective gene delivery systems. However, transduction efficiency in skeletal muscles varies between AAV serotypes, with the underlying factors poorly understood. We hypothesized that myofiber-specific tropism differs between AAV serotypes.METHODS: We developed a quantitative histology procedure and generated myofiber pattern maps for four myosin heavy chain (MyHC) isotypes. We compared myofiber pattern maps between AAV6 or AAV9 injected tibialis anterior muscle in mice. We correlated MyHC expression with AAV-derived green fluorescence protein (GFP) expression using statistical models.RESULTS: We found that MyHC-2x expressing myofibers display a significantly higher preference for AAV transduction, whereas MyHC-2b expressing myofibers negatively correlated with AAV transduction. In addition, we show that AAV9-mediated transduction is enriched in myofibers expressing MyHC-1 and MyHC-1/2a. Moreover, AAV9-mediated transduction can predominantly be predicted by the expression of MyHC isotypes. In contrast, AAV6 transduction can be predicted by myofiber size but not by myofiber types.CONCLUSIONS: Our findings identify differences between AAV6 and AAV9 for myofiber-type preferences, which could be an underlying factor for mosaic transduction of skeletal muscle. Adjusting AAV serotype for specific muscle conditions can therefore improve transduction efficacy in clinical applications.

Details

Database :
OAIster
Journal :
Skeletal Muscle vol.5 (2015) p.37 [ISSN 2044-5040]
Notes :
DOI: 10.1186/s13395-015-0064-4, Skeletal Muscle vol.5 (2015) p.37 [ISSN 2044-5040], English
Publication Type :
Electronic Resource
Accession number :
edsoai.ocn961157802
Document Type :
Electronic Resource