By John N. Abelson, Melvin I. Simon, M. Ian Phillips
Antisense know-how is the facility to govern gene expression inside of mammalian cells delivering strong experimental methods for the learn of gene functionality and gene rules. for instance, equipment that inhibit gene expression allow reports which probe the traditional functionality of a particular product inside a mobilephone. Such technique can be utilized in lots of disciplines corresponding to pharmacology, oncology, genetics, cellphone biology, developmental biology, molecular biology, biochemistry, and neurosciences. This quantity may be a very vital software in biomedical-oriented learn. The severely acclaimed laboratory average for greater than 40 years, Methods in Enzymology is likely one of the so much hugely revered guides within the box of biochemistry. in view that 1955, every one quantity has been eagerly awaited, usually consulted, and praised via researchers and reviewers alike. Now with greater than three hundred volumes (all of them nonetheless in print), the sequence comprises a lot fabric nonetheless correct today--truly a necessary book for researchers in all fields of lifestyles sciences.
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Additional resources for Antisense Technology, Part A, General Methods, Methods of Delivery, and RNA Studies
Chem. 272, 18191 (1997). 70 H. Wu, W. F. Lima, and S. T. Crooke, Antisense Nucleic Acid Drug Dev. 8, 53 (1998). 70a H. Wu and S. T. Crooke, unpublished observations. 69  PROGRESS IN ANTISENSE TECHNOLOGY 17 Selection of Optimal RNA-Binding Site It has been amply demonstrated that a signiﬁcant fraction of every RNA species is not accessible to phosphorothioate oligodeoxynucleotides in a fashion that permits antisense effects (for a review, see Crooke71). Thus, substantial efforts have been directed to the development of methods that might predict optimal sites for binding within RNA species.
Perform sufﬁcient pharmacokinetics to deﬁne rational dosing schedules for pharmacological studies. When control oligonucleotides display surprising activities, determine the mechanisms involved. Molecular Mechanisms of Antisense Drugs Occupancy-Only Mediated Mechanisms Classic competitive antagonists are thought to alter biological activities because they bind to receptors preventing natural agonists from binding the inducing normal biological processes. Binding of oligonucleotides to speciﬁc sequences may inhibit the interaction of the RNA with proteins, other nucleic acids, or other factors required for essential steps in the intermediary metabolism of the RNA or its utilization by the cell.
Ryder, Nucleic Acids Res. 17, 3373 (1989). 52 F. Morvan, B. Rayner, and J. L. Imbach, Anticancer Drug Des. 6, 521 (1991). 53 C. Gagnor, B. Rayner, J. P. Leonetti, J. L. Imbach, and B. Lebleu, Nucleic Acids Res. 17, 5107 (1989). 54 L. J. Maher, III, B. Wold, and P. B. Dervan, Science 245, 725 (1989). 55 P. S. Miller, in ‘‘Oligodeoxynucleotides: Antisense Inhibitors of Gene Expression’’ (J. S. ), p. 79. CRC Press, Boca Raton, FL, 1989. 56 C. A. -C. Cheng, Science 261, 1004 (1993). 57 C. Cazenave, C.
Antisense Technology, Part A, General Methods, Methods of Delivery, and RNA Studies by John N. Abelson, Melvin I. Simon, M. Ian Phillips