Vector genome loss and epigenetic modifications mediate decline in transgene expression of AAV5 vectors produced in mammalian and insect cells

Autor: Britta Handyside, Ashrafali Mohamed Ismail, Lening Zhang, Bridget Yates, Lin Xie, Choong-Ryoul Sihn, Ryan Murphy, Taren Bouwman, Chan Kyu Kim, Rolando De Angelis, Omair A. Karim, Nicole L. McIntosh, Michael Xavier Doss, Shilpa Shroff, Erno Pungor, Vikas S. Bhat, Sherry Bullens, Stuart Bunting, Sylvia Fong
Rok vydání: 2022
Předmět:
Zdroj: Molecular Therapy. 30:3570-3586
ISSN: 1525-0016
DOI: 10.1016/j.ymthe.2022.11.001
Popis: Recombinant adeno-associated virus (rAAV) vectors are often produced in HEK293 or Spodoptera frugiperda (Sf)-based cell lines. We compared expression profiles of "oversized" (∼5,000 bp) and "standard-sized" (4,600 bp) rAAV5-human α1-antitrypsin (rAAV5-hA1AT) vectors manufactured in HEK293 or Sf cells and investigated molecular mechanisms mediating expression decline. C57BL/6 mice received 6 × 10
Databáze: OpenAIRE