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The IUP Journal of Biotechnology :
A Survey on Antisense Oligonucleotides Efficacy Prediction
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Developments in the sequencing of human genome have led to the use of short fragments of nucleic acid, commonly known as oligonucleotides as curative agents. Over the past three decades, antisense oligonucleotide technology has emerged as a valid approach to selectively modulate gene expression. However, in practice, only a few complementary oligonucleotides, show effective suppression. The reasons and the various forms of experiments have been dealt with in the work. The primary goal of this survey is to emphasize the different techniques used for antisense oligonucleotide efficacy prediction.

Antisense oligonucleotides typically consist of 15-30 nucleotides that inhibit gene expression by complementary basepairing by using the Watson-Crick hybridization to target mRNA. Hybridization between the antisense oligonucleotide and its target mRNA is a fundamental activity of the antisense process. This can be viewed as a two-step process of nucleation at an accessible site and elongation. The result is a simple mechanistic blocking of the ribosome, thereby inhibiting protein translation or activation of RNase H enzyme that subsequently induces cleavage and degradation of mRNA, thus blocking the transfer of genetic information from DNA to protein. RNase H is a ubiquitous enzyme that hydrolyzes the RNA strand of an RNA/DNA duplex. The other mechanisms that can knock down gene expression apart from RNase H mediated cleavage are interference with translation or splicing and destabilization of the target mRNA. Several antisense compounds for disease treatment have been evaluated in clinical trials including tumors, AIDS, hepatitis C, asthma, high cholesterol, diabetes, and ocular neovascular disease (Sun et al., 2006). In 1998, Vitravene (Isis Pharmaceuticals, Carlsbad, CA) became the first antisense drug approved by the Food and Drug administration (Dias and Stein, 2002). It is used to treat cytomegalovirus retinitis in AIDS patients.

Methods that can predict the efficacy of potential oligos are important, since they would reduce the cost of carrying out antisense knock down experiments.

 
 
 

A Survey on Antisense Oligonucleotides Efficacy Prediction,antisense, oligonucleotide, experiments, enzyme, cleavage, translation, protein, cholesterol, clinical, cytomegalovirus, destabilization, duplex, elongation, fundamental, fragments, Hybridization, mechanisms, neovascular, nucleotides, nucleation, asthma, Pharmaceuticals, RNADNA