Gene regulatory and gene editing tools and their applications for retinal diseases and neuroprotection: From proof-of-concept to clinical trial
Gene editing and gene regulatory fields are continuously developing new and safer tools that move beyond the initial CRISPR/Cas9 technology. As more advanced applications are emerging, it becomes crucial to understand and establish more complex gene regulatory and editing tools for efficient gene th...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-10-01
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| Series: | Frontiers in Neuroscience |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fnins.2022.924917/full |
| _version_ | 1811251845915475968 |
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| author | Halit Yusuf Altay Fatma Ozdemir Ferdows Afghah Zeynep Kilinc Mehri Ahmadian Markus Tschopp Markus Tschopp Cavit Agca Cavit Agca |
| author_facet | Halit Yusuf Altay Fatma Ozdemir Ferdows Afghah Zeynep Kilinc Mehri Ahmadian Markus Tschopp Markus Tschopp Cavit Agca Cavit Agca |
| author_sort | Halit Yusuf Altay |
| collection | DOAJ |
| description | Gene editing and gene regulatory fields are continuously developing new and safer tools that move beyond the initial CRISPR/Cas9 technology. As more advanced applications are emerging, it becomes crucial to understand and establish more complex gene regulatory and editing tools for efficient gene therapy applications. Ophthalmology is one of the leading fields in gene therapy applications with more than 90 clinical trials and numerous proof-of-concept studies. The majority of clinical trials are gene replacement therapies that are ideal for monogenic diseases. Despite Luxturna’s clinical success, there are still several limitations to gene replacement therapies including the size of the target gene, the choice of the promoter as well as the pathogenic alleles. Therefore, further attempts to employ novel gene regulatory and gene editing applications are crucial to targeting retinal diseases that have not been possible with the existing approaches. CRISPR-Cas9 technology opened up the door for corrective gene therapies with its gene editing properties. Advancements in CRISPR-Cas9-associated tools including base modifiers and prime editing already improved the efficiency and safety profile of base editing approaches. While base editing is a highly promising effort, gene regulatory approaches that do not interfere with genomic changes are also becoming available as safer alternatives. Antisense oligonucleotides are one of the most commonly used approaches for correcting splicing defects or eliminating mutant mRNA. More complex gene regulatory methodologies like artificial transcription factors are also another developing field that allows targeting haploinsufficiency conditions, functionally equivalent genes, and multiplex gene regulation. In this review, we summarized the novel gene editing and gene regulatory technologies and highlighted recent translational progress, potential applications, and limitations with a focus on retinal diseases. |
| first_indexed | 2024-04-12T16:26:11Z |
| format | Article |
| id | doaj.art-0d9cc5af924747e4b563b6456a8112c2 |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-04-12T16:26:11Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj.art-0d9cc5af924747e4b563b6456a8112c22022-12-22T03:25:22ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2022-10-011610.3389/fnins.2022.924917924917Gene regulatory and gene editing tools and their applications for retinal diseases and neuroprotection: From proof-of-concept to clinical trialHalit Yusuf Altay0Fatma Ozdemir1Ferdows Afghah2Zeynep Kilinc3Mehri Ahmadian4Markus Tschopp5Markus Tschopp6Cavit Agca7Cavit Agca8Molecular Biology, Genetics and Bioengineering Program, Sabanci University, Istanbul, TurkeyMolecular Biology, Genetics and Bioengineering Program, Sabanci University, Istanbul, TurkeyMolecular Biology, Genetics and Bioengineering Program, Sabanci University, Istanbul, TurkeyMolecular Biology, Genetics and Bioengineering Program, Sabanci University, Istanbul, TurkeyMolecular Biology, Genetics and Bioengineering Program, Sabanci University, Istanbul, TurkeyDepartment of Ophthalmology, Cantonal Hospital Aarau, Aarau, SwitzerlandDepartment of Ophthalmology, Inselspital, Bern University Hospital, University of Bern, Bern, SwitzerlandMolecular Biology, Genetics and Bioengineering Program, Sabanci University, Istanbul, TurkeyNanotechnology Research and Application Center (SUNUM), Sabanci University, Istanbul, TurkeyGene editing and gene regulatory fields are continuously developing new and safer tools that move beyond the initial CRISPR/Cas9 technology. As more advanced applications are emerging, it becomes crucial to understand and establish more complex gene regulatory and editing tools for efficient gene therapy applications. Ophthalmology is one of the leading fields in gene therapy applications with more than 90 clinical trials and numerous proof-of-concept studies. The majority of clinical trials are gene replacement therapies that are ideal for monogenic diseases. Despite Luxturna’s clinical success, there are still several limitations to gene replacement therapies including the size of the target gene, the choice of the promoter as well as the pathogenic alleles. Therefore, further attempts to employ novel gene regulatory and gene editing applications are crucial to targeting retinal diseases that have not been possible with the existing approaches. CRISPR-Cas9 technology opened up the door for corrective gene therapies with its gene editing properties. Advancements in CRISPR-Cas9-associated tools including base modifiers and prime editing already improved the efficiency and safety profile of base editing approaches. While base editing is a highly promising effort, gene regulatory approaches that do not interfere with genomic changes are also becoming available as safer alternatives. Antisense oligonucleotides are one of the most commonly used approaches for correcting splicing defects or eliminating mutant mRNA. More complex gene regulatory methodologies like artificial transcription factors are also another developing field that allows targeting haploinsufficiency conditions, functionally equivalent genes, and multiplex gene regulation. In this review, we summarized the novel gene editing and gene regulatory technologies and highlighted recent translational progress, potential applications, and limitations with a focus on retinal diseases.https://www.frontiersin.org/articles/10.3389/fnins.2022.924917/fullCRISPR-Casrare diseasesretinagene therapyTALEzinc finger |
| spellingShingle | Halit Yusuf Altay Fatma Ozdemir Ferdows Afghah Zeynep Kilinc Mehri Ahmadian Markus Tschopp Markus Tschopp Cavit Agca Cavit Agca Gene regulatory and gene editing tools and their applications for retinal diseases and neuroprotection: From proof-of-concept to clinical trial Frontiers in Neuroscience CRISPR-Cas rare diseases retina gene therapy TALE zinc finger |
| title | Gene regulatory and gene editing tools and their applications for retinal diseases and neuroprotection: From proof-of-concept to clinical trial |
| title_full | Gene regulatory and gene editing tools and their applications for retinal diseases and neuroprotection: From proof-of-concept to clinical trial |
| title_fullStr | Gene regulatory and gene editing tools and their applications for retinal diseases and neuroprotection: From proof-of-concept to clinical trial |
| title_full_unstemmed | Gene regulatory and gene editing tools and their applications for retinal diseases and neuroprotection: From proof-of-concept to clinical trial |
| title_short | Gene regulatory and gene editing tools and their applications for retinal diseases and neuroprotection: From proof-of-concept to clinical trial |
| title_sort | gene regulatory and gene editing tools and their applications for retinal diseases and neuroprotection from proof of concept to clinical trial |
| topic | CRISPR-Cas rare diseases retina gene therapy TALE zinc finger |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2022.924917/full |
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