Read e-book online RNA Interference: Application to Drug Discovery and PDF

By Paul H. Johnson, John J. Rossi

ISBN-10: 0471771511

ISBN-13: 9780471771517

RNA Interference: program to Drug Discovery and demanding situations to Pharmaceutical improvement presents a common review of this swiftly rising box, with a powerful emphasis on concerns and elements which are very important to a drug improvement staff. the 1st half covers extra common history of RNA interference and its software in drug discovery. within the moment half, the booklet addresses siRNA (small interfering RNA), a pharmaceutically effective shape, and its use and supply in therapeutics besides production and supply elements.

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3 Three major action mechanisms of ASOs. When an ASO is taken up by the cell, it can hybridize to its target RNA. Formation of an RNA–ASO heteroduplex may induce (1) activation of the ubiquitous cellular RNase H, leading to selective degradation of the target mRNA, (2) steric blocking, resulting in translation arrest, and/or (3) inhibition of pre-mRNA splicing. In principle, ASOs may be used to selectively knock down any target gene expression. P1: TIX c02 JWBS053-Johnson November 9, 2010 21:2 Printer Name: Yet to Come ARTIFICIAL MODULATION OF GENE EXPRESSION 21 mechanism for downregulation of the target gene expression by most types of ASOs, translation blocking by ASO can be significant as well.

The majority of the listed antisense drug candidates belong to the first-generation phosphorothioate oligonucleotides. 6), if certain conditions (such as DNA sequence, ionic strength, and media pH) are met. Formation of DNA triplexes was first 28 Company Name Isis Pharmaceuticals NeoPharm Genta Inc. AVI Biopharm AVI Biopharm OncoGenex Technologies, Lorus Therapeutics Topigen Pharmaceuticals Antisense Pharma Isis Pharmaceuticals Isis Pharmaceuticals Isis Pharmaceuticals Antisense Therapeutics Eli Lilly Eli Lilly Vitravene LRrafAON-ETU Genasense RESTEN-MP AVI-4126 OGX-011 GTI-2040 TPI-ASM8 AP 12009 Alicaforsen ISIS 301012 ISIS 113715 ATL1102 LY2181308 LY2275796 FDA approved Phase I Phase III Phase II Phase I Phase II Phase II Phase II Phase II Phase II Phase II Phase II Phase II Phase I Phase I Peripheral CMV retinitis Advanced cancer Advanced melanoma Cardiovascular restenosis Cancer Lung cancer Kidney cancer Asthma Pancreatic cancer Ulcerative colitis High cholesterol Diabetes Multiple sclerosis Cancer Cancer Clinical Stage Lead Indication Some ASOs as Therapeutics in Human Clinical Trials.

A CRE DNA decoy consisting of the consensus palindromic sequence TGACGTCA was shown to compete with CRE enhancers for binding transcription factors and interfered with CRE- and AP-1-directed transcription. The decoy could enter the cell, inhibit transcription of specific CRE-directed genes, and inhibit tumor cell growth both in vitro and in vivo [27]. Noncancerous cells were not affected by the decoy. In a microarray (a signal transduction pathway array containing 1152 genes) experiment [28] with the CRE DNA decoy treatment on tumors, ∼10% of the genes on the array showed altered expression of >2-fold.

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RNA Interference: Application to Drug Discovery and Challenges to Pharmaceutical Development by Paul H. Johnson, John J. Rossi

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