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dc.rights.licenseAl consultar y hacer uso de este recurso, está aceptando las condiciones de uso establecidas por los autores.es_CO
dc.contributor.advisorRestrepo Restrepo, Silvia 
dc.contributor.authorMéndez Ortega, María Catalina
dc.date.accessioned2018-09-28T07:47:08Z
dc.date.available2018-09-28T07:47:08Z
dc.date.issued2010
dc.identifier.urihttp://hdl.handle.net/1992/11137
dc.description.abstractInhibition of HIV-1 by RNA interference can be achieved by the expression of short hairpin RNAs (shRNAs) targeting conserved sequences. We designed shRNAs against HIV-1 reverse transcriptase considering the variability of conserved regions within the retrovirus reverse transcriptase conserved domain cd01645, where the RNA dependent DNA polymerase activity of the enzyme resides. HXB2 (K03455) genome was used to choose regions with conserved residues important for enzyme activity. Regions were identified in multiple alignments from naive and drug-resistant isolates. A script was developed that predicted silencing efficiency based on previously reported parameters and that could identify highly frequent nucleotide combinations in a 21 base-long window within these regions. Higher number of sequence combinations was found in alignments from resistant isolates. shRNAs targeting reverse transcriptase active site residues W24 and P25 had scores over 7. Three-dimensional structural analyses from wild-type and resistant enzymes consistent with enormous variability explain the difficulties in finding a perfect region for RNAi mediated silencing. For clinical purposes, HIV-1 variability is an obstacle for efficient silencing from shRNAs designed towards a consensus sequence as there are too many functional variants of the enzyme. We suggest a complementary therapy using a combinatorial approach consisting of a mix of shRNAs targeting the most frequent viral variants from 1214 naïve genomes and 1381 from resistant variants, during a highly active antiretroviral therapy regimen.
dc.formatapplication/pdfes_CO
dc.format.extent70 hojases_CO
dc.language.isoenges_CO
dc.publisherUniandeses_CO
dc.sourceinstname:Universidad de los Andeses_CO
dc.sourcereponame:Repositorio Institucional Sénecaes_CO
dc.titleshRNA desing based on natural and drug induced variability targeting conserved regions from HIV reverse transcriptasees_CO
dc.typeTrabajo de grado - Maestríaes_CO
dc.publisher.programMaestría en Ciencias Biológicases_CO
dc.rights.accessRightsopenAccess
dc.subject.keywordVIH - Investigacioneses_CO
dc.subject.keywordInterferencia de ARN - Investigacioneses_CO
dc.subject.keywordTerapia de gen - Investigacioneses_CO
dc.subject.keywordTerapia antirretroviral altamente activa - Investigacioneses_CO
dc.publisher.facultyFacultad de Cienciases_CO
dc.publisher.departmentDepartamento de Biologíaes_CO
dc.type.versionpublishedVersion
dc.type.versionpublishedVersiones_CO
dc.description.degreenameMagíster en Ciencias Biológicases_CO
dc.description.degreelevelMaestríaes_CO


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