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Variables and Strategies in Development of Therapeutic Post-Transcriptional Gene Silencing Agents
Post-transcriptional gene silencing (PTGS) agents such as ribozymes, RNAi and antisense have substantial potential for gene therapy of human retinal degenerations. These technologies are used to knockdown a specific target RNA and its cognate protein. The disease target mRNA may be a mutant mRNA cau...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi Publishing Corporation
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3138052/ https://www.ncbi.nlm.nih.gov/pubmed/21785698 http://dx.doi.org/10.1155/2011/531380 |
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author | Sullivan, Jack M. Yau, Edwin H. Kolniak, Tiffany A. Sheflin, Lowell G. Taggart, R. Thomas Abdelmaksoud, Heba E. |
author_facet | Sullivan, Jack M. Yau, Edwin H. Kolniak, Tiffany A. Sheflin, Lowell G. Taggart, R. Thomas Abdelmaksoud, Heba E. |
author_sort | Sullivan, Jack M. |
collection | PubMed |
description | Post-transcriptional gene silencing (PTGS) agents such as ribozymes, RNAi and antisense have substantial potential for gene therapy of human retinal degenerations. These technologies are used to knockdown a specific target RNA and its cognate protein. The disease target mRNA may be a mutant mRNA causing an autosomal dominant retinal degeneration or a normal mRNA that is overexpressed in certain diseases. All PTGS technologies depend upon the initial critical annealing event of the PTGS ligand to the target RNA. This event requires that the PTGS agent is in a conformational state able to support hybridization and that the target have a large and accessible single-stranded platform to allow rapid annealing, although such platforms are rare. We address the biocomplexity that currently limits PTGS therapeutic development with particular emphasis on biophysical variables that influence cellular performance. We address the different strategies that can be used for development of PTGS agents intended for therapeutic translation. These issues apply generally to the development of PTGS agents for retinal, ocular, or systemic diseases. This review should assist the interested reader to rapidly appreciate critical variables in PTGS development and facilitate initial design and testing of such agents against new targets of clinical interest. |
format | Online Article Text |
id | pubmed-3138052 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-31380522011-07-22 Variables and Strategies in Development of Therapeutic Post-Transcriptional Gene Silencing Agents Sullivan, Jack M. Yau, Edwin H. Kolniak, Tiffany A. Sheflin, Lowell G. Taggart, R. Thomas Abdelmaksoud, Heba E. J Ophthalmol Review Article Post-transcriptional gene silencing (PTGS) agents such as ribozymes, RNAi and antisense have substantial potential for gene therapy of human retinal degenerations. These technologies are used to knockdown a specific target RNA and its cognate protein. The disease target mRNA may be a mutant mRNA causing an autosomal dominant retinal degeneration or a normal mRNA that is overexpressed in certain diseases. All PTGS technologies depend upon the initial critical annealing event of the PTGS ligand to the target RNA. This event requires that the PTGS agent is in a conformational state able to support hybridization and that the target have a large and accessible single-stranded platform to allow rapid annealing, although such platforms are rare. We address the biocomplexity that currently limits PTGS therapeutic development with particular emphasis on biophysical variables that influence cellular performance. We address the different strategies that can be used for development of PTGS agents intended for therapeutic translation. These issues apply generally to the development of PTGS agents for retinal, ocular, or systemic diseases. This review should assist the interested reader to rapidly appreciate critical variables in PTGS development and facilitate initial design and testing of such agents against new targets of clinical interest. Hindawi Publishing Corporation 2011 2011-06-30 /pmc/articles/PMC3138052/ /pubmed/21785698 http://dx.doi.org/10.1155/2011/531380 Text en Copyright © 2011 Jack M. Sullivan et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Review Article Sullivan, Jack M. Yau, Edwin H. Kolniak, Tiffany A. Sheflin, Lowell G. Taggart, R. Thomas Abdelmaksoud, Heba E. Variables and Strategies in Development of Therapeutic Post-Transcriptional Gene Silencing Agents |
title | Variables and Strategies in Development of Therapeutic Post-Transcriptional Gene Silencing Agents |
title_full | Variables and Strategies in Development of Therapeutic Post-Transcriptional Gene Silencing Agents |
title_fullStr | Variables and Strategies in Development of Therapeutic Post-Transcriptional Gene Silencing Agents |
title_full_unstemmed | Variables and Strategies in Development of Therapeutic Post-Transcriptional Gene Silencing Agents |
title_short | Variables and Strategies in Development of Therapeutic Post-Transcriptional Gene Silencing Agents |
title_sort | variables and strategies in development of therapeutic post-transcriptional gene silencing agents |
topic | Review Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3138052/ https://www.ncbi.nlm.nih.gov/pubmed/21785698 http://dx.doi.org/10.1155/2011/531380 |
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