Antisense Technology: Applications Part B by Abelson J.N., Simon M.I., Phillips I.M.

By Abelson J.N., Simon M.I., Phillips I.M.

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H. Eckel, Diabetes 48(1), 223 (1999). 6K. Anwer, M. Shi, M. F. French, S. R. Muller, W. Chen, Q. Liu, B. L. Proctor, J. Wang, R. J. Mumper, A. Singhal, A. P. Rolland, and H. W. Alila, Hum. Gene Ther. 9(5), 659 (1998). 34 ANTISENSE RECEPTOR TARGETS 13] polyvinylpyrrolidone. Tokui et al. 7 injected plasmid with interleukin 5 (IL5) cDNA into the soleus muscle of mice, resulting in increased serum levels of IL-5 and an increased percentage of eosinophils in white blood cells, 2 weeks after injection.

The rep gene encodes proteins responsible for viral replication, whereas cap encodes capsid proteins VP1-3. Each ITR forms a T-shaped hairpin structure. These terminal repeats are the only essential cis components of the A A V for packaging the virus. Therefore, the A A V can be used as a vector with all viral coding sequences removed and replaced by the cassette of genes for delivery. Three viral promoters have been identified and named p5, p19, and p40, according to their map position. Transcription from p5 and p19 results in production of Rep proteins, and transcription from p40 produces the capsid proteins.

17 H. Fakhrai, O. Dorigo, D. L. Shawler, H. Lin, D. Mercola, K. L. Black, I. Royston, and R. E. Sobel, Proc. Natl. Acad. Sci. A. 93(7), 2909 (1996). 18 M. J. McCluskie, Y. Chu, J. L. Xia, J. Jessee, G. Gebyehu, and H. L. Davis, Antisense Nucleic Acid Drug. Dev. 8(5), 401 (1998). 36 ANTISENSERECEPTORTARGETS [3] Generally, plasmid D N A is considered safer to use than viral vectors, but expression is usually less efficient and shorter lasting. Some improvement has been shown by using different carriers and/or complexing agents, such as liposomes, polyvinylpyrrolidone, or starburst dendrimers.

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