a strategy for adenovirus vector targeting with a secreted single chain antibody腺病毒载体的策略定位和分泌单链抗体.pdfVIP

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a strategy for adenovirus vector targeting with a secreted single chain antibody腺病毒载体的策略定位和分泌单链抗体.pdf

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a strategy for adenovirus vector targeting with a secreted single chain antibody腺病毒载体的策略定位和分泌单链抗体

A Strategy for Adenovirus Vector Targeting with a Secreted Single Chain Antibody 1,2 3 3 2 Joel N. Glasgow *, Galina Mikheeva , Victor Krasnykh , David T. Curiel 1 Division of Cardiovascular Disease, Departments of Medicine, Obstetrics and Gynecology, Pathology, Surgery, and the Gene Therapy Center, University of Alabama at Birmingham, Birmingham, Alabama, United States of America, 2 Division of Human Gene Therapy, Departments of Medicine, Obstetrics and Gynecology, Pathology, Surgery, and the Gene Therapy Center, University of Alabama at Birmingham, Birmingham, Alabama, United States of America, 3 Department of Experimental Diagnostic Imaging, University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America Abstract Background: Successful gene therapy will require targeted delivery vectors capable of self-directed localization. In this regard, the use of antibodies or single chain antibody fragments (scFv) in conjunction with adenovirus (Ad) vectors remains an attractive means to achieve cell-specific targeting. However, a longstanding barrier to the development of Ad vectors with genetically incorporated scFvs has been the biosynthetic incompatibility between Ad capsid proteins and antibody- derived species. Specifically, scFv require posttranslational modifications not available to Ad capsid proteins due to their cytoplasmic routing during protein synthesis and virion assembly. Methodology/Principal Findings: We have therefore sought to develop scFv-targeted Ad vectors using a secreted scFv that undergoes the requisite posttranslational modifications and is trafficked for secretion. Formation of the scFv-targeted Ad vector is achieved via highly specific association of the Ad virion and a targeting scFv employing synt