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The Landscape of Non-Viral Gene Augmentation Strategies for Inherited Retinal Diseases
Inherited retinal diseases (IRDs) are a heterogeneous group of disorders causing progressive loss of vision, affecting approximately one in 1000 people worldwide. Gene augmentation therapy, which typically involves using adeno-associated viral vectors for delivery of healthy gene copies to affected...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7956638/ https://www.ncbi.nlm.nih.gov/pubmed/33652562 http://dx.doi.org/10.3390/ijms22052318 |
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author | Toualbi, Lyes Toms, Maria Moosajee, Mariya |
author_facet | Toualbi, Lyes Toms, Maria Moosajee, Mariya |
author_sort | Toualbi, Lyes |
collection | PubMed |
description | Inherited retinal diseases (IRDs) are a heterogeneous group of disorders causing progressive loss of vision, affecting approximately one in 1000 people worldwide. Gene augmentation therapy, which typically involves using adeno-associated viral vectors for delivery of healthy gene copies to affected tissues, has shown great promise as a strategy for the treatment of IRDs. However, the use of viruses is associated with several limitations, including harmful immune responses, genome integration, and limited gene carrying capacity. Here, we review the advances in non-viral gene augmentation strategies, such as the use of plasmids with minimal bacterial backbones and scaffold/matrix attachment region (S/MAR) sequences, that have the capability to overcome these weaknesses by accommodating genes of any size and maintaining episomal transgene expression with a lower risk of eliciting an immune response. Low retinal transfection rates remain a limitation, but various strategies, including coupling the DNA with different types of chemical vehicles (nanoparticles) and the use of electrical methods such as iontophoresis and electrotransfection to aid cell entry, have shown promise in preclinical studies. Non-viral gene therapy may offer a safer and effective option for future treatment of IRDs. |
format | Online Article Text |
id | pubmed-7956638 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-79566382021-03-16 The Landscape of Non-Viral Gene Augmentation Strategies for Inherited Retinal Diseases Toualbi, Lyes Toms, Maria Moosajee, Mariya Int J Mol Sci Review Inherited retinal diseases (IRDs) are a heterogeneous group of disorders causing progressive loss of vision, affecting approximately one in 1000 people worldwide. Gene augmentation therapy, which typically involves using adeno-associated viral vectors for delivery of healthy gene copies to affected tissues, has shown great promise as a strategy for the treatment of IRDs. However, the use of viruses is associated with several limitations, including harmful immune responses, genome integration, and limited gene carrying capacity. Here, we review the advances in non-viral gene augmentation strategies, such as the use of plasmids with minimal bacterial backbones and scaffold/matrix attachment region (S/MAR) sequences, that have the capability to overcome these weaknesses by accommodating genes of any size and maintaining episomal transgene expression with a lower risk of eliciting an immune response. Low retinal transfection rates remain a limitation, but various strategies, including coupling the DNA with different types of chemical vehicles (nanoparticles) and the use of electrical methods such as iontophoresis and electrotransfection to aid cell entry, have shown promise in preclinical studies. Non-viral gene therapy may offer a safer and effective option for future treatment of IRDs. MDPI 2021-02-26 /pmc/articles/PMC7956638/ /pubmed/33652562 http://dx.doi.org/10.3390/ijms22052318 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Toualbi, Lyes Toms, Maria Moosajee, Mariya The Landscape of Non-Viral Gene Augmentation Strategies for Inherited Retinal Diseases |
title | The Landscape of Non-Viral Gene Augmentation Strategies for Inherited Retinal Diseases |
title_full | The Landscape of Non-Viral Gene Augmentation Strategies for Inherited Retinal Diseases |
title_fullStr | The Landscape of Non-Viral Gene Augmentation Strategies for Inherited Retinal Diseases |
title_full_unstemmed | The Landscape of Non-Viral Gene Augmentation Strategies for Inherited Retinal Diseases |
title_short | The Landscape of Non-Viral Gene Augmentation Strategies for Inherited Retinal Diseases |
title_sort | landscape of non-viral gene augmentation strategies for inherited retinal diseases |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7956638/ https://www.ncbi.nlm.nih.gov/pubmed/33652562 http://dx.doi.org/10.3390/ijms22052318 |
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