The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.
A myocardium tropic adeno-associated virus (AAV) evolved by DNA shuffling and in vivo selection
Open accessAbstract
To engineer gene vectors that target striated muscles after systemic delivery, we constructed a random library of adeno-associated virus (AAV) by shuffling the capsid genes of AAV serotypes 1 to 9, and screened for muscle-targeting capsids by direct in vivo panning after tail vein injection in mice. After 2 rounds of in vivo selection, a capsid gene named M41 was retrieved mainly based on its high frequency in the muscle and low frequency in the liver. Structural analyses revealed that the AAVM41 capsid is a recombinant of AAV1, 6, 7, and 8 with a mosaic capsid surface and a conserved capsid interior. AAVM41 was then subjected to a side-by-side comparison to AAV9, the most robust AAV for systemic heart and muscle gene delivery; to AAV6, a parental AAV with strong muscle tropism. After i.v. delivery of reporter genes, AAVM41 was found more efficient than AAV6 in the heart and muscle, and was similar to AAV9 in the heart but weaker in the muscle. In fact, the myocardium showed the highest gene expression among all tissues tested in mice and hamsters after systemic AAVM41 delivery. However, gene transfer in non-muscle tissues, mainly the liver, was dramatically reduced. AAVM41 was further tested in a genetic cardiomyopathy hamster model and achieved efficient long-term δ-sarcoglycan gene expression and rescue of cardiac functions. Thus, direct in vivo panning of capsid libraries is a simple tool for the de-targeting and retargeting of viral vector tissue tropisms facilitated by acquisition of desirable sequences and properties.
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Selection and evaluation of clinically relevant AAV variants in a xenograft liver model
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Metadata
- Authors
- Yang, L., Jiang, J., Drouin, L. M., Agbandje-Mckenna, M., Chen, C., Qiao, C., Pu, D., Hu, X., Wang, D.-Z., Li, J., & Xiao, X.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2009-03-10
- Volume
- 106
- Issue
- 10
- Pages
- 3946-3951
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2167659424
- Cited by
- 210
- References
- 8
- FWCI
- 10.52
- Type
- journal article
- Language
- en
- Open access
- green
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- Yang, L., Jiang, J., Drouin, L. M., Agbandje-Mckenna, M., Chen, C., Qiao, C., Pu, D., Hu, X., Wang, D.-Z., Li, J., & Xiao, X. (2009). A myocardium tropic adeno-associated virus (AAV) evolved by DNA shuffling and in vivo selection. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0813207106
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