Epigenetics - Gene silencing.
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2009-01
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Abstract
The discovery of the mechanism of RNA interference by ds RNA by Prof. Andrew Fire and Prof. Craig Mello in 1998, gave them the Nobel Prize in 2006. This discovery revealed a new mechanism for gene regulation through “gene silencing” at the transcriptional level (TGS) or at the post-transcriptional level (PTGS), which play a key role in many essential cellular processes. Today dsRNA is used as a powerful tool to experimentally elucidate the function of essentially any gene in a cell. The immense impact of the discovery of RNA interference (RNAi) on biomedical research and its novel medical applications in the future are reviewed in this article, with particular stress on therapeutic applications of radio-labeled antisense oligonucleotides (RASONs) for diagnosis and treatment of various cancers and neurodegenerative diseases by “gene silencing”. Antisense oligonucleotides (ASONs) can also modulate alternative splicing which 74% of all human genes undergo. The most effective targeting strategy employs simultaneous blocking SnRNP binding sites and splice junctions. Correction of splicing by ASONs can be used to silence mutations causing aberrant splicing as in thalassemia, Duchenne muscular dystrophy and cystic fibrosis. ©
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Lele R D. Epigenetics - Gene silencing. Journal of the Association of Physicians of India. 2009 Jan; 57(): 60-66.