دورية أكاديمية
Novel human liver-tropic AAV variants define transferable domains that markedly enhance the human tropism of AAV7 and AAV8
| العنوان: | Novel human liver-tropic AAV variants define transferable domains that markedly enhance the human tropism of AAV7 and AAV8 |
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| المؤلفون: | Marti Cabanes-Creus, Renina Gale Navarro, Erhua Zhu, Grober Baltazar, Sophia H.Y. Liao, Matthieu Drouyer, Anais K. Amaya, Suzanne Scott, Loan Hanh Nguyen, Adrian Westhaus, Matthias Hebben, Laurence O.W. Wilson, Adrian J. Thrasher, Ian E. Alexander, Leszek Lisowski |
| المصدر: | Molecular Therapy: Methods & Clinical Development, Vol 24, Iss , Pp 88-101 (2022) |
| بيانات النشر: | Elsevier, 2022. |
| سنة النشر: | 2022 |
| المجموعة: | LCC:Genetics LCC:Cytology |
| مصطلحات موضوعية: | AAV, adeno-associated vectors, bioengineering, bioengineered vectors, gene therapy, liver-tropic, Genetics, QH426-470, Cytology, QH573-671 |
| الوصف: | Recent clinical successes have intensified interest in using adeno-associated virus (AAV) vectors for therapeutic gene delivery. The liver is a key clinical target, given its critical physiological functions and involvement in a wide range of genetic diseases. Here, we report the bioengineering of a set of next-generation AAV vectors, named AAV-SYDs (where “SYD” stands for Sydney, Australia), with increased human hepato-tropism in a liver xenograft mouse model repopulated with primary human hepatocytes. We followed a two-step process that staggered directed evolution and domain-swapping approaches. Using DNA-family shuffling, we first mapped key AAV capsid regions responsible for efficient human hepatocyte transduction in vivo. Focusing on these regions, we next applied domain-swapping strategies to identify and study key capsid residues that enhance primary human hepatocyte uptake and transgene expression. Our findings underscore the potential of AAV-SYDs as liver gene therapy vectors and provide insights into the mechanism responsible for their enhanced transduction profile. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2329-0501 |
| Relation: | http://www.sciencedirect.com/science/article/pii/S2329050121001832; https://doaj.org/toc/2329-0501 |
| DOI: | 10.1016/j.omtm.2021.11.011 |
| URL الوصول: | https://doaj.org/article/1abf6bd1dabc4da8b922b404440e19d1 |
| رقم الأكسشن: | edsdoj.1abf6bd1dabc4da8b922b404440e19d1 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 23290501 |
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| DOI: | 10.1016/j.omtm.2021.11.011 |