By Stanley T. Crooke
Broadly revised and up to date, Antisense Drug know-how: ideas, options, and functions, moment variation displays the logarithmic growth made some time past 4 years of oligonucleotide-based remedies, and, particularly, antisense therapeutics and study. reading classes realized from the medical trials of first new release medications, the ebook evaluates the know-how as an entire and provides new instructions and avenues of analysis and improvement. Divided into 5 elements, the ebook starts with an intensive creation to the mechanism of antisense drug motion together with the RNase H mechanism, small RNA silencing pathways, and the capability therapeutics of splice switching oligonucleotides. best researchers reveal the fundamentals of oligonucleotide therapeutics partially by means of delineating medicinal chemistry, pharmacokinetics, and supply routes resembling liposomal formulations for nucleic acid delivery. half 3 information hybridization established medications and considers the dramatic advances represented via 2’ methoxyethyl chimeric antisense inhibitors and duplex RNA medications. different chemical sessions of substances and mechanisms of motion are defined partly 4 with additional discussions on bettering the second one new release antisense medicines. the ultimate half delves deeply into healing purposes. Contributing authors research the opportunity of antisense medicines for the relief of cardiovascular ailments, metabolic ailments, inflammatory illnesses, melanoma, neurological issues, and immune modulation. featuring a hugely special, lucid dialogue of the striking advances within the box, Antisense Drug know-how: rules, recommendations, and purposes, moment variation offers the platform for researchers to proceed to aggressively pursue the nice chance represented through this interesting expertise.
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Additional info for Antisense Drug Technology: Principles, Strategies, and Applications, Second Edition
At present, the proposition that facilitated hybridization is important in determining the effectiveness of antisense drugs is largely conjectural. However, this area has benefited from virtually no research and now that the tools are available, progress in this important area should be forthcoming. 5 Levels of Target RNA Although it is theoretically possible that the concentration, transcriptional rate, or stability of a target RNA may influence the effectiveness of antisense drugs, at least for antisense drugs that work via the RNase H mechanism, it has been experimentally determined that RNA concentration and transcription rate do not affect their performance .
RNA editing is effected by the deamination of either adenosine to inosine or cytosine to uridine. In both cases, the sequence of the RNA is modified from that originally transcribed from the gene. RNA editing has been shown to play significant roles by introducing new codons that may initiate translation, prematurely stop translation, alter splicing, or influence other steps in the metabolism and utilization of RNAs (for review, see [64,65]). Given how frequently RNA editing occurs and its substantial importance to normal and pathophysiological process, it seems likely that the processes should influence the activities of antisense drugs.
Given the low concentrations of pre- and m-RNAs in cells and the high intracellular concentrations of antisense drugs achieved, the receptor concentration can be eliminated and drug effect should be dependant only on drug concentration. Transcriptional rate should have no effect because receptor concentrations are irrelevant. Similarly, m-RNA decay rate should have no effect. 6 Terminating Mechanism The first step in the induction of pharmacodymic effects by an antisense drug is hybridization to its cognate sequence or receptor.
Antisense Drug Technology: Principles, Strategies, and Applications, Second Edition by Stanley T. Crooke