Developing a second-generation clinical candidate AAV vector for gene therapy of familial hypercholesterolemia.

ABSTRACT: Gene therapy for hypercholesterolemia offers the potential to sustainably ameliorate disease for life with a single dose. In this study, we demonstrate the combinatorial effects of codon and vector optimization, which significantly improve the efficacy of an adeno-associated virus (AAV) vector in the low-density lipoprotein receptor (LDLR)-deficient mouse model (Ldlr ^-/-, Apobec1 ^-/- double knockout [DKO]). This study investigated vector efficacy following the combination of intervening sequence 2 (IVS2) of the human beta-globin gene and codon optimization with the previously developed gain-of-function, human LDLR triple-mutant variant (hLDLR-L318D/K809R/C818A) in the treatment of homozygous familial hypercholesterolemia (HoFH). Vector doses as low as 3 

SUBMITTER: Wang L 

PROVIDER: S-EPMC8237527 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature