Development and Validation of AAV-Mediated Liver, Liver-VAT, and Liver-Brain SORT and Therapeutic Regulation of FASN in Hepatic De Novo Lipogenesis.

ABSTRACT: Hepatic lipogenesis combined with elevated endoplasmic reticulum (ER) stress is central to non-alcoholic steatohepatitis (NASH). However, the therapeutic targeting of key molecules is considerably less accomplished. Adeno-associated virus (AAV)-mediated gene therapies offer a new solution for various human ailments. Comprehensive bio-functional validation studies are essential to assess the impact of AAVs in the target organ for developing both preclinical and clinical gene therapy programs. Here, we have established a robust and efficient protocol for high-titer AAV production to enable detailed Selective ORgan Targeting (SORT) of AAV1, 5, 7, and 8 in vivo. Our results for in vivo SORT showed single organ (liver) targeting by AAV8, no organ targeting by AAV1, and dual organ transduction (

SUBMITTER: Bhadury R 

PROVIDER: S-EPMC11899426 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature