Current Targeting Strategies for Adenovirus Vectors in Cancer Gene Therapy

X.-L.      Yao; S.      Nakagawa; J.-Q.      Gao

Abstract

Adenovirus vectors (Adv) are the most frequently used vectors in gene therapy research, especially in cancer gene therapy. However, despite encouraging preclinical and early clinical results, the successful clinical utility of gene therapy has not yet been fully realized. Challenges to clinical trial success for targeted Adv include inefficient Advmediated gene transfer (because many tumor cells lack Adv receptors), poor transduction in tumor tissues after systemic administration, accumulation and undesirable transgene expression in the liver. This review summarizes current targeting strategies for Adv to overcome these obstacles. Strategies include transductional selectivity through genetic modification of viral coat proteins, transcriptional selectivity by means of tumor-specific promoters, and selective biodistribution from conjugation with targeting ligands or polymers such as polyethylene glycol (PEG). Furthermore, combining selective biodistribution and active targeting ligands such as proteins, antibodies and peptides is an intriguing and promising approach that will also be covered in this review. These studies have provided new insights into our understanding of the utility of Adv in cancer gene therapy.

Keywords: Adenovirus vector, gene therapy, cancer therapy, targeting, gene delivery, tumor-specific promoter, polyethylene glycol, targeting ligand, glutamic, –, pyruvic transaminase, polyethylenimine, arginine-grafted bio-reducible polymer, PEGylated Adv, telomerase reverse transcriptase, gastrin releasing peptide, carcinoembryonic antigen