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By S. T. Crooke (auth.), Stanley T. Crooke M.D., Ph.D. (eds.)

ISBN-10: 3642587852

ISBN-13: 9783642587856

ISBN-10: 3642637302

ISBN-13: 9783642637308

Antisense expertise can result in dramatic alterations within the treatment of many ailments and will offer instruments to dissect pharmacological tactics and to verify the jobs of varied genes. during this quantity, development within the knowing of antisense expertise and its use in developing new medicines is mentioned. strength caveats, pitfalls and obstacles of the know-how also are provided. within the following few years the velocity at which new molecular goals can be pointed out increases exponentially because the sequencing of the human genome and of different genomes proceeds.

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Liver, kidney, bone marrow, skeletal muscle, and skin accumulate the highest percentage of a dose, but other tissues display small quantities of drug (COSSUM et al. 1993,1994). No evidence of significant penetration of the blood-brain barrier has been reported. The rates of incorporation and clearance from tissues vary as a function of the organ studied, with liver accumulating drug most rapidly (20% of a dose within 1-2 h) and other tissues accumulating drug more slowly. , terminal half-life from liver: 62h, from renal medulla: 156h.

Oligonucleotides designed to bind to a 17- 8 S. T. CROOKE nucleotide loop in Xenopus 28 S RNA required for ribosome stability and protein synthesis inhibited protein synthesis when injected into Xenopus oocytes (SAXENA and ACKERMAN 1990). 8S RNA inhibited protein synthesis in rabbit reticulocyte and wheat germ systems (WALKER et al. 1990). II. Occupancy Activated Destabilization RNA molecules regulate their own metabolism. A number of structural features of RNA are known to influence stability, various processing events, subcellular distribution and transport.

___~~==::::J~AAAA+ -.. ( \... ___-===== _ Effeclson -Catabolism of mRNA Translational Arrest Basic Principles of Antisense Therapeutics 9 RNA. For example, the synthesis of SV40 T-antigen was reported to be most sensitive to an oligonucleotide linked to polylysine and targeted to the 5'-cap site of RNA (WESTERMANN et al. 1989). However, once again, in no published study has this putative mechanism been rigorously demonstrated. In fact, in no published study have the oligonucleotides been shown to bind to the sequences for which they were designed.

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Antisense Research and Application by S. T. Crooke (auth.), Stanley T. Crooke M.D., Ph.D. (eds.)

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