Role of Fiber Shaft Length in Tumor Targeting with Ad5/3 Vectors.

ABSTRACT: Desmoglein 2 (DSG2) is overexpressed in many epithelial cancers and therefore represents a target receptor for oncolytic viruses, including Ad5/3-based viruses. For most Ad serotypes, the receptor-binding fiber is composed of tail, shaft, and knob domains. Here, we investigated the role of the fiber shaft in Ad5/3 tumor transduction in vitro and in human DSG2-transgenic mice carrying human DSG2^high tumors. DSG2tg mice express DSG2 in a pattern similar to humans. We constructed Ad5/3L (with the "long" Ad5 shaft) and Ad5/3S (with the "short" Ad3 shaft) expressing GFP or luciferase. In in vitro studies we found that coagulation factor X, which is known to mediate undesired hepatocyte transduction of Ad5, enhances the transduction of Ad5/3(L), but not the transduction of Ad5/3(S). W

SUBMITTER: Richter M 

PROVIDER: S-EPMC9690795 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature