High-level protein production in erythroid cells derived from in vivo transduced hematopoietic stem cells.

ABSTRACT: We developed an in vivo hematopoietic stem cell (HSC) transduction approach that involves HSC mobilization from the bone marrow into the peripheral bloodstream and the IV injection of an integrating, helper-dependent adenovirus (HDAd5/35⁺⁺) vector system. HDAd5/35⁺⁺ vectors target human CD46, a receptor that is abundantly expressed on primitive HSCs. Transgene integration is achieved by a hyperactive Sleeping Beauty transposase (SB100x) and transgene marking in peripheral blood cells can be increased by in vivo selection. Here we directed transgene expression to HSC-derived erythroid cells using β-globin regulatory elements. We hypothesized that the abundance and systemic distribution of erythroid cells can be harnessed for high-level production of therapeutic protein

SUBMITTER: Wang H 

PROVIDER: S-EPMC6784527 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature