Genome editing for scalable production of alloantigen-free lentiviral vectors for in vivo gene therapy.

ABSTRACT: Lentiviral vectors (LV) are powerful and versatile vehicles for gene therapy. However, their complex biological composition challenges large-scale manufacturing and raises concerns for in vivo applications, because particle components and contaminants may trigger immune responses. Here, we show that producer cell-derived polymorphic class-I major histocompatibility complexes (MHC-I) are incorporated into the LV surface and trigger allogeneic T-cell responses. By disrupting the beta-2 microglobulin gene in producer cells, we obtained MHC-free LV with substantially reduced immunogenicity. We introduce this targeted editing into a novel stable LV packaging cell line, carrying single-copy inducible vector components, which can be reproducibly converted into high-yield LV producers upon

SUBMITTER: Milani M 

PROVIDER: S-EPMC5666310 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature