Enhancing Lentiviral and Alpharetroviral Transduction of Human Hematopoietic Stem Cells for Clinical Application.

ABSTRACT: Ex vivo retroviral gene transfer into CD34⁺ hematopoietic stem and progenitor cells (HSPCs) has demonstrated remarkable clinical success in gene therapy for monogenic hematopoietic disorders. However, little attention has been paid to enhancement of culture and transduction conditions to achieve reliable effects across patient and disease contexts and to maximize potential vector usage and reduce treatment cost. We systematically tested three HSPC culture media manufactured to cGMP and eight previously described transduction enhancers (TEs) to develop a state-of-the-art clinically applicable protocol. Six TEs enhanced lentiviral (LV) and five TEs facilitated alpharetroviral (ARV) CD34⁺ HSPC transduction when used alone. Combinatorial TE application tested with

SUBMITTER: Schott JW 

PROVIDER: S-EPMC6629974 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature