Biomod/2013/BITS

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  <h1 class="title">Biomimetics at nanoscale: DNA origami to deliver IRES aptamers using HCV as a template</h1>
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<iframe width="560" height="315" align:center src="#" frameborder="0" allowfullscreen></iframe>
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<h2>Abstract</h2>
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<div class="intro">With its worldwide distribution, Hepatitis C Virus (HCV) infects about 3-4 million people every year of which the chronically infected ones are at a risk of developing liver cirrhosis, hepatic failure or hepatocellular carcinoma. The limited availability and poor tolerance towards antiviral therapy and interferon with ribavirin (nucleoside inhibitor) demands a different approach towards targeting the HCV infection. Research indicates that the HCV genome translation is under the control of the Internal Ribosomal Entry Site (IRES) which mediates cap-independent internal initiation of HCV polyprotein translation thereby making it a quintessential target to halt and thereby curb the infection. Nucleic acid ligands generated using SELEX (Systematic Evolution of Ligands by EXponential enrichment) called aptamers, are the recent class of molecules showing immense potential to be crafted for binding to multiple different targets. First proposed by Seeman and started by Rothemund, DNA origami is based on the principle that a long ssDNA scaffold can be molded into any desired shape using staples. With this method of tailoring DNA nanostructures, the self assembling property of nucleic acids would be exploited for the delivery of IRES specific aptamers to the HCV infected cells. We designed a cylindrical nanostructure mimicking HCV by attaching E1-E2 conjugate peptide sequences, facilitating the entry via endosomal pathway; and by using pH sensitive detachable lids to release the IRES aptamers packed inside the nanostructure to the infected cells. The aptamer based silencing of viral translation will in turn prevent the assembly of new viroids and serve as a mechanism to control the HCV infection.</div>
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Revision as of 13:35, 16 October 2013







Biomimetics at nanoscale: DNA origami to deliver IRES aptamers using HCV as a template


<iframe width="560" height="315" align:center src="#" frameborder="0" allowfullscreen></iframe>


Abstract

With its worldwide distribution, Hepatitis C Virus (HCV) infects about 3-4 million people every year of which the chronically infected ones are at a risk of developing liver cirrhosis, hepatic failure or hepatocellular carcinoma. The limited availability and poor tolerance towards antiviral therapy and interferon with ribavirin (nucleoside inhibitor) demands a different approach towards targeting the HCV infection. Research indicates that the HCV genome translation is under the control of the Internal Ribosomal Entry Site (IRES) which mediates cap-independent internal initiation of HCV polyprotein translation thereby making it a quintessential target to halt and thereby curb the infection. Nucleic acid ligands generated using SELEX (Systematic Evolution of Ligands by EXponential enrichment) called aptamers, are the recent class of molecules showing immense potential to be crafted for binding to multiple different targets. First proposed by Seeman and started by Rothemund, DNA origami is based on the principle that a long ssDNA scaffold can be molded into any desired shape using staples. With this method of tailoring DNA nanostructures, the self assembling property of nucleic acids would be exploited for the delivery of IRES specific aptamers to the HCV infected cells. We designed a cylindrical nanostructure mimicking HCV by attaching E1-E2 conjugate peptide sequences, facilitating the entry via endosomal pathway; and by using pH sensitive detachable lids to release the IRES aptamers packed inside the nanostructure to the infected cells. The aptamer based silencing of viral translation will in turn prevent the assembly of new viroids and serve as a mechanism to control the HCV infection.












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