Hepatotoxicity and Toxicology of In Vivo Lentiviral Vector Administration in Healthy and Liver-Injury Mouse Models.

ABSTRACT: General safety and toxicology assessments supporting in vivo lentiviral vector-based therapeutic development are sparse. We have previously demonstrated the efficacy of a lentiviral vector expressing fumarylacetoacetate hydrolase (LV-FAH) to cure animal models of hereditary tyrosinemia type 1. Therefore, we performed a complete preclinical toxicological evaluation of LV-FAH, in a large cohort (n = 20/group) of wildtype mice and included matched groups of N-nitrosodiethylamine/carbon tetrachloride (DEN/CCl₄)-induced liver injury mice to assess specific toxicity in fibrotic liver tissue. Mice receiving LV-FAH alone (10⁹ TU/mouse) or in combination with DEN/CCl₄ presented clinically similar to control animals, with only slight reductions in total

SUBMITTER: Kaiser RA 

PROVIDER: S-EPMC6589498 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature