Rescue of infant progressive familial intrahepatic cholestasis type 3 mice by repeated dosing of AAV gene therapy.

ABSTRACT:

Background & aims

Gene therapy using recombinant adeno-associated virus (rAAV) vector carrying multidrug resistance protein 3 (MDR3) coding sequence (AAV8-MDR3) represents a potential curative treatment for progressive familial intrahepatic cholestasis type 3 (PFIC3), which presents in early childhood. However, patients with the severest form of PFIC3 should receive treatment early after detection to prevent irreversible hepatic fibrosis leading ultimately to liver transplantation or death. This represents a challenge for rAAV-based gene therapy because therapeutic efficacy is expected to wane as rAAV genomes are lost owing to hepatocyte division, and the formation of AAV-specific neutralising antibodies precludes re-administration. Here, we tested a strategy of vector re-administr

SUBMITTER: Weber ND 

PROVIDER: S-EPMC10121466 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature