Intracellular Antibodies (Intrabodies) and Their Therapeutic Potential

作者: A. S. -Y. Lo , Q. Zhu , W. A. Marasco

DOI: 10.1007/978-3-540-73259-4_15

关键词:

摘要: Combining exquisite specificity and high antigen-binding affinity, intrabodies have been used as a biotechnological tool to interrupt, modulate, or define the functions of wide range target antigens at posttranslational level. An intrabody is an antibody that has designed be expressed intracellularly can directed specific antigen present in various subcellular locations including cytosol, nucleus, endoplasmic reticulum (ER), mitochondria, peroxisomes, plasma membrane trans-Golgi network (TGN) through frame fusion with intracellular trafficking/localization peptide sequences. Although different forms, most commonly format singlechain (scFv Ab) created by joining variable domains heavy light chain interchain linker (ICL), often 15 amino acid (GGGGS)(3) between (VH) (VL) chains. Intrabodies research cancer, HIV, autoimmune disease, neurodegenerative transplantation. Clinical application mainly hindered availability robust gene delivery system(s) cell delivery. This review will discuss several methods selection, strategies cellular targeting, recent successful examples applications. Taking advantage affinity for its antigen, virtually unlimited diversity available molecular techniques are emerging promising tools generate phenotypic knockouts, manipulate biological processes, obtain more thorough understanding functional genomics.

参考文章(138)
A.M. Mhashilkar, J. Bagley, S.Y. Chen, A.M. Szilvay, D.G. Helland, W.A. Marasco, Inhibition of HIV-1 Tat-mediated LTR transactivation and HIV-1 infection by anti-Tat single chain intrabodies. The EMBO Journal. ,vol. 14, pp. 1542- 1551 ,(1995) , 10.1002/J.1460-2075.1995.TB07140.X
A. Nissim, H.R. Hoogenboom, I.M. Tomlinson, G. Flynn, C. Midgley, D. Lane, G. Winter, Antibody fragments from a 'single pot' phage display library as immunochemical reagents. The EMBO Journal. ,vol. 13, pp. 692- 698 ,(1994) , 10.1002/J.1460-2075.1994.TB06308.X
Reuven Levin, Abner M. Mhashilkar, Tatyana Dorfman, Anatoly Bukovsky, Christy Zani, Jessamyn Bagley, Jorma Hinkula, Mattias Niedrig, Jan Albert, Britta Wahren, Heinrich G. Göttlinger, Wayne A. Marasco, Inhibition of early and late events of the HIV-1 replication cycle by cytoplasmic Fab intrabodies against the matrix protein, p17. Molecular Medicine. ,vol. 3, pp. 96- 110 ,(1997) , 10.1007/BF03401802
R.R. Beerli, W. Wels, N.E. Hynes, Intracellular expression of single chain antibodies reverts ErbB-2 transformation Journal of Biological Chemistry. ,vol. 269, pp. 23931- 23936 ,(1994) , 10.1016/S0021-9258(19)51027-4
Qian YUAN, Kathryn L. STRAUCH, Roy R. LOBB, Martin E. HEMLER, Intracellular single-chain antibody inhibits integrin VLA-4 maturation and function Biochemical Journal. ,vol. 318, pp. 591- 596 ,(1996) , 10.1042/BJ3180591
Simoy Goldstein, Paul Zhou, Deepanker Tewari, Abner Louis Notkins, Krishnakumar Devadas, Cells Transfected with a Non-Neutralizing Antibody Gene Are Resistant to HIV Infection: Targeting the Endoplasmic Reticulum and Trans-Golgi Network Journal of Immunology. ,vol. 160, pp. 1489- 1496 ,(1998)
O Ikeda-Tanaka, H I Yamanaka, T Inoue, Chicken monoclonal antibody isolated by a phage display system. Journal of Immunology. ,vol. 157, pp. 1156- 1162 ,(1996)
Hassan M.E Azzazy, W.Edward Highsmith, Phage display technology: clinical applications and recent innovations. Clinical Biochemistry. ,vol. 35, pp. 425- 445 ,(2002) , 10.1016/S0009-9120(02)00343-0
Andrew Fire, SiQun Xu, Mary K. Montgomery, Steven A. Kostas, Samuel E. Driver, Craig C. Mello, Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans Nature. ,vol. 391, pp. 806- 811 ,(1998) , 10.1038/35888