IMMUNOLOGYIntrabody-based gene therapeutic strategyZhu, Jian-guo; Lin, Yuan; Li, BenqiangAuthor Information Shanghai Key Laboratory of Veterinary Biotechnology, School of Agriculture and Biology, Shanghai Jiaotong University, Shanghai, China. Correspondence to Jian-guo Zhu, #56, Agriculture and Biology Building, No. 800, Dongchuan Road, Minhang Area, Shanghai 200240, China. Tel: +86 21 34206367; e-mail: [email protected] Received 27 November, 2010 Revised 10 August, 2011 Accepted 20 June, 2012 Reviews in Medical Microbiology: October 2012 - Volume 23 - Issue 4 - p 76-81 doi: 10.1097/MRM.0b013e32835736a6 Buy Metrics Abstract Intrabody-based gene therapeutic strategy has been used successfully in the functional knockdown of target molecules in cells, and is shown to be beneficial in cells and animal models of HIV infection, promising future application of intrabody gene therapy against viral infections. Intrabodies can block translocation of molecules from the endoplasmic reticulum to the cell surface causing functional inhibition of the target proteins, and can disrupt biological signaling pathways of target proteins by interfering with normal protein–protein or protein–DNA interactions to examine biological function of molecules. Intrabody therapy may also be applicable to prion diseases due to misfolded proteins. However, the efficient cytoplasmic expression of single-chain variable fragments (scFvs) is generally confronted with folding problems, low solubility and a high tendency for aggregation, most likely because of the reducing environment of the cell cytoplasm. These problems can be artificially improved via a series of mutations, fusing the scFv with other fragments, or developing intracellular screening steps to isolate highly stable and soluble frameworks of intrabody from an appropriate library. © 2012 Lippincott Williams & Wilkins, Inc.