دورية أكاديمية
Bioengineered Viral Platform for Intramuscular Passive Vaccine Delivery to Human Skeletal Muscle
| العنوان: | Bioengineered Viral Platform for Intramuscular Passive Vaccine Delivery to Human Skeletal Muscle |
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| المؤلفون: | Nicole K. Paulk, Katja Pekrun, Gregory W. Charville, Katie Maguire-Nguyen, Michael N. Wosczyna, Jianpeng Xu, Yue Zhang, Leszek Lisowski, Bryan Yoo, Jose G. Vilches-Moure, Gordon K. Lee, Joseph B. Shrager, Thomas A. Rando, Mark A. Kay |
| المصدر: | Molecular Therapy: Methods & Clinical Development, Vol 10, Iss , Pp 144-155 (2018) |
| بيانات النشر: | Elsevier, 2018. |
| سنة النشر: | 2018 |
| المجموعة: | LCC:Genetics LCC:Cytology |
| مصطلحات موضوعية: | Genetics, QH426-470, Cytology, QH573-671 |
| الوصف: | Skeletal muscle is ideal for passive vaccine administration as it is easily accessible by intramuscular injection. Recombinant adeno-associated virus (rAAV) vectors are in consideration for passive vaccination clinical trials for HIV and influenza. However, greater human skeletal muscle transduction is needed for therapeutic efficacy than is possible with existing serotypes. To bioengineer capsids with therapeutic levels of transduction, we utilized a directed evolution approach to screen libraries of shuffled AAV capsids in pools of surgically resected human skeletal muscle cells from five patients. Six rounds of evolution were performed in various muscle cell types, and evolved variants were validated against existing muscle-tropic serotypes rAAV1, 6, and 8. We found that evolved variants NP22 and NP66 had significantly increased primary human and rhesus skeletal muscle fiber transduction from surgical explants ex vivo and in various primary and immortalized myogenic lines in vitro. Importantly, we demonstrated reduced seroreactivity compared to existing serotypes against normal human serum from 50 adult donors. These capsids represent powerful tools for human skeletal muscle expression and secretion of antibodies from passive vaccines. Keywords: AAV, passive vaccine, directed evolution, skeletal muscle, human, screen, functional transduction |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2329-0501 |
| العلاقة: | http://www.sciencedirect.com/science/article/pii/S2329050118300536Test; https://doaj.org/toc/2329-0501Test |
| DOI: | 10.1016/j.omtm.2018.06.001 |
| الوصول الحر: | https://doaj.org/article/ba3cc380d053477da8b6a626ff9c0d2bTest |
| رقم الانضمام: | edsdoj.ba3cc380d053477da8b6a626ff9c0d2b |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 23290501 |
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| DOI: | 10.1016/j.omtm.2018.06.001 |