Lentivector Iterations and Pre-Clinical Scale-Up/Toxicity Testing: Targeting Mobilized CD34⁺ Cells for Correction of Fabry Disease.

ABSTRACT: Fabry disease is a rare lysosomal storage disorder (LSD). We designed multiple recombinant lentivirus vectors (LVs) and tested their ability to engineer expression of human α-galactosidase A (α-gal A) in transduced Fabry patient CD34⁺ hematopoietic cells. We further investigated the safety and efficacy of a clinically directed vector, LV/AGA, in both ex vivo cell culture studies and animal models. Fabry mice transplanted with LV/AGA-transduced hematopoietic cells demonstrated α-gal A activity increases and lipid reductions in multiple tissues at 6 months after transplantation. Next we found that LV/AGA-transduced Fabry patient CD34⁺ hematopoietic cells produced even higher levels of α-gal A activity than normal CD34⁺ hematopoietic cells. We successfully tra

SUBMITTER: Huang J 

PROVIDER: S-EPMC5453867 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature