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Oligonucleotides: The Next Big Challenge For Analytical Chemistry - George Okafo & Chris Bevan

Sep 13 2010 Read 7414 Times

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Research and development of oligonucleotides as therapeutic medicines is experiencing exponential growth and interest within academia, the biotechnology and pharmaceutical industries [1]. This has largely been driven
by several key historical events including:

1. The regulatory approval of the first antisense oligonucleotide (ASO) for cytomegalovirus infection Vitravene® (1998)[2],
2. Approval of Macugen®, an aptamer for treatment of wet macular degeneration (2005) [3]
3. The discovery by Drs Andrew Fire and Craig Mello of gene silencing by RNA interference (RNAi) (published 1998, Nobel Prize, 2006).[4]

RNAi technology has been used to validate gene targets, and both RNAi and ASO technologies have been used to interfere with targets that are considered non-druggable by traditional small molecule interventions [5]. The early Nobel Prize-winning work by Fire and Mello demonstrated that some genes in C.elegans can be switched off by the introduction of double stranded small interfering RNA (siRNA) to block the normal translation of a specific messenger RNA to the protein product [4]. This early identification of the process has been extended to mammalian cells and the molecular process characterized.

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