Production of therapeutic levels of human FIX-R338L by engineered B cells using GMP-compatible medium.

ABSTRACT: B cells can differentiate into plasmablast and plasma cells, capable of producing antibodies for decades. Gene editing using zinc-finger nucleases (ZFN) enables the engineering of B cells capable of secreting sustained and high levels of therapeutic proteins. In this study, we established an advanced in vitro good manufacturing practice-compatible culturing system characterized by robust and consistent expansion rate, high viability, and efficient B cell differentiation. Using this process, an optimized B cell editing protocol was developed by combining ZFN/adeno-associated virus 6 technology to achieve site-specific insertion of the human factor IX R338L Padua into the silent TRAC locus. In vitro analysis revealed high levels of secreted human immunoglobulins and huma

SUBMITTER: David M 

PROVIDER: S-EPMC10543988 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature