Harnessing whole human liver ex situ normothermic perfusion for preclinical AAV vector evaluation.

ABSTRACT: Developing clinically predictive model systems for evaluating gene transfer and gene editing technologies has become increasingly important in the era of personalized medicine. Liver-directed gene therapies present a unique challenge due to the complexity of the human liver. In this work, we describe the application of whole human liver explants in an ex situ normothermic perfusion system to evaluate a set of fourteen natural and bioengineered adeno-associated viral (AAV) vectors directly in human liver, in the presence and absence of neutralizing human sera. Under non-neutralizing conditions, the recently developed AAV variants, AAV-SYD12 and AAV-LK03, emerged as the most functional variants in terms of cellular uptake and transgene expression. However, when assessed in the presence of hu

SUBMITTER: Cabanes-Creus M 

PROVIDER: S-EPMC10940703 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature