derivation of a triple mosaic adenovirus for cancer gene therapy推导的三重马赛克腺病毒癌基因治疗.pdfVIP

Derivation of a Triple Mosaic Adenovirus for Cancer Gene Therapy 1,2 1 1 1,3 1 Yizhe Tang , Hongju Wu , Hideyo Ugai , Qiana L. Matthews , David T. Curiel * 1 Division of Human Gene Therapy, Departments of Medicine, Pathology, Surgery, and Obstetrics and Gynecology, and the Gene Therapy Center, University of Alabama at Birmingham, Birmingham, Alabama, United States of America, 2 Vision Science Graduate Program, University of Alabama at Birmingham, Birmingham, Alabama, United States of America, 3 Center for AIDS Research, University of Alabama at Birmingham, Birmingham, Alabama, United States of America Abstract A safe and efficacious cancer medicine is necessary due to the increasing population of cancer patients whose particular diseases cannot be cured by the currently available treatment. Adenoviral (Ad) vectors represent a promising therapeutic medicine for human cancer therapy. However, several improvements are needed in order for Ad vectors to be effective cancer therapeutics, which include, but are not limited to, improvement of cellular uptake, enhanced cancer cell killing activity, and the capability of vector visualization and tracking once injected into the patients. To this end, we attempted to develop an Ad as a multifunctional platform incorporating targeting, imaging, and therapeutic motifs. In this study, we explored the utility of this proposed platform by generating an Ad vector containing the poly-lysine (pK), the herpes simplex virus type 1 (HSV-1) thymidine kinase (TK), and the monomeric red fluorescent protein (mRFP1) as targeting, tumor cell killing, and imaging motifs, respectively. Our study herein demonstrates the generation of the triple mosaic Ad vector with pK