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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...

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Autores principales: Sullivan, Jack M., Yau, Edwin H., Kolniak, Tiffany A., Sheflin, Lowell G., Taggart, R. Thomas, Abdelmaksoud, Heba E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2011
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.
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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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