AAV-Mediated Targeting of the Activin A-ACVR1^R206H Signaling in Fibrodysplasia Ossificans Progressiva.

ABSTRACT: Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare genetic disorder characterized by progressive disabling heterotopic ossification (HO) at extra-skeletal sites. Here, we developed adeno-associated virus (AAV)-based gene therapy that suppresses trauma-induced HO in FOP mice harboring a heterozygous allele of human ACVR1^R206H (Acvr1^R206H/+) while limiting the expression in non-skeletal organs such as the brain, heart, lung, liver, and kidney. AAV gene therapy carrying the combination of codon-optimized human ACVR1 (ACVR1^opt) and artificial miRNAs targeting Activin A and its receptor ACVR1^R206H ablated the aberrant activation of BMP-Smad1/5 signaling and the osteogenic differentiation of Acvr1^R206H/+ skelet

SUBMITTER: Yang YS 

PROVIDER: S-EPMC10526456 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature