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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/5/2318 |
| _version_ | 1797395190508421120 |
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| author | Lyes Toualbi Maria Toms Mariya Moosajee |
| author_facet | Lyes Toualbi Maria Toms Mariya Moosajee |
| author_sort | Lyes Toualbi |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-09T00:31:50Z |
| format | Article |
| id | doaj.art-cc208ba23c324ba781726ae65dce6b3e |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T00:31:50Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-cc208ba23c324ba781726ae65dce6b3e2023-12-11T18:30:17ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-02-01225231810.3390/ijms22052318The Landscape of Non-Viral Gene Augmentation Strategies for Inherited Retinal DiseasesLyes Toualbi0Maria Toms1Mariya Moosajee2UCL Institute of Ophthalmology, London EC1V 9EL, UKUCL Institute of Ophthalmology, London EC1V 9EL, UKUCL Institute of Ophthalmology, London EC1V 9EL, UKInherited 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.https://www.mdpi.com/1422-0067/22/5/2318inherited retinal diseasenon-viral gene therapyplasmid DNAnanoparticlestransfectionphotoreceptors |
| spellingShingle | Lyes Toualbi Maria Toms Mariya Moosajee The Landscape of Non-Viral Gene Augmentation Strategies for Inherited Retinal Diseases International Journal of Molecular Sciences inherited retinal disease non-viral gene therapy plasmid DNA nanoparticles transfection photoreceptors |
| 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 | inherited retinal disease non-viral gene therapy plasmid DNA nanoparticles transfection photoreceptors |
| url | https://www.mdpi.com/1422-0067/22/5/2318 |
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