Prime Editing, a Novel Genome-Editing Tool That May Surpass Conventional CRISPR-Cas9
Background: Genome editing mediated by clustered regularly interspaced short palindromic repeat -CRISPR-Cas- was first reported using cell lines in 2012, and since then, its applications in other systems have steadily increased. However, this approach still needs improvement and optimization. Prime...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Mary Ann Liebert
2021-01-01
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| Series: | Re:GEN Open |
| Subjects: | |
| Online Access: | https://www.liebertpub.com/doi/full/10.1089/REGEN.2021.0016 |
| _version_ | 1797346078507401216 |
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| author | Adriana Ochoa-Sanchez Gabriela Perez-Sanchez A. Marianna Torres-Ledesma Juan Pablo R. Valdez Gabriel Rinaldi B?rbara B. Moguel B?rbara B. Moguel Christian Molina-Aguilar Christian Molina-Aguilar |
| author_facet | Adriana Ochoa-Sanchez Gabriela Perez-Sanchez A. Marianna Torres-Ledesma Juan Pablo R. Valdez Gabriel Rinaldi B?rbara B. Moguel B?rbara B. Moguel Christian Molina-Aguilar Christian Molina-Aguilar |
| author_sort | Adriana Ochoa-Sanchez |
| collection | DOAJ |
| description | Background: Genome editing mediated by clustered regularly interspaced short palindromic repeat -CRISPR-Cas- was first reported using cell lines in 2012, and since then, its applications in other systems have steadily increased. However, this approach still needs improvement and optimization. Prime Editing (PE) was originally proposed by Anzalone and colleagues in 2019, who showed significant lower rates of "off target" effects compared to conventional CRISPR-Cas9.
Objectives: In this review, we describe and compare the "conventional" CRISPR-Cas9 system with a novel homology-directed repair-independent editing approach called Prime Editing (PE).
Methods: Numerous recent publications involving the PE molecular mechanism for targeted-mutagenesis, advantages, limitations, and applications of the approach in different biomedicine fields were reviewed.
Results: From the literature, it appears that PE neither relies on DSB nor needs HDR with exogenous donor DNA templates, which shows the clinical potential of PEs in correcting a broad range of mutations for genetic diseases. Four generations of PE mechanisms have been developed, reaching higher efficiency from one generation to the next one. However, reviewed studies support that PE also introduces new challenges such as unwanted mutations mediated by the double nicking strategy required for the PE3's efficiency, the selection of the optimal combination of PBS and RT templates, and the limitation of large DNA insertions that conventional CRISPR-Cas9 is capable of.
Conclusion: The reviewed literature demonstrate that genome editing-based PE is a promising technology aiming at decreasing the common undesirable effects associated with conventional genome editing approaches such as CRISPR-Cas9 or BE. Even though progress has been made to improve the efficiency of the genome editing by the PE ribonucleo-protein complex, further research is required to optimize PE tools and maximize its efficiency. |
| first_indexed | 2024-03-08T11:26:39Z |
| format | Article |
| id | doaj.art-41838f7dbdb84441994172a70cd957af |
| institution | Directory Open Access Journal |
| issn | 2766-2705 |
| language | English |
| last_indexed | 2024-03-08T11:26:39Z |
| publishDate | 2021-01-01 |
| publisher | Mary Ann Liebert |
| record_format | Article |
| series | Re:GEN Open |
| spelling | doaj.art-41838f7dbdb84441994172a70cd957af2024-01-26T05:12:24ZengMary Ann LiebertRe:GEN Open2766-27052021-01-0111758210.1089/REGEN.2021.0016Prime Editing, a Novel Genome-Editing Tool That May Surpass Conventional CRISPR-Cas9Adriana Ochoa-Sanchez0Gabriela Perez-Sanchez1A. Marianna Torres-Ledesma2Juan Pablo R. Valdez3Gabriel Rinaldi4B?rbara B. Moguel5B?rbara B. Moguel6Christian Molina-Aguilar7Christian Molina-Aguilar8Escuela de Ingenier?a y Ciencias, Tecnologico de MonterreyEscuela de Ingenier?a y Ciencias, Tecnologico de MonterreyEscuela de Ingenier?a y Ciencias, Tecnologico de MonterreyEscuela de Ingenier?a y Ciencias, Tecnologico de MonterreyWellcome Sanger Institute, Wellcome Genome CampusEscuela de Ingenier?a y Ciencias, Tecnologico de MonterreyLaboratorio Internacional de Investigaci?n Sobre el Genoma Humano, Universidad Nacional Aut?noma de M?xicoEscuela de Ingenier?a y Ciencias, Tecnologico de MonterreyLaboratorio Internacional de Investigaci?n Sobre el Genoma Humano, Universidad Nacional Aut?noma de M?xicoBackground: Genome editing mediated by clustered regularly interspaced short palindromic repeat -CRISPR-Cas- was first reported using cell lines in 2012, and since then, its applications in other systems have steadily increased. However, this approach still needs improvement and optimization. Prime Editing (PE) was originally proposed by Anzalone and colleagues in 2019, who showed significant lower rates of "off target" effects compared to conventional CRISPR-Cas9. Objectives: In this review, we describe and compare the "conventional" CRISPR-Cas9 system with a novel homology-directed repair-independent editing approach called Prime Editing (PE). Methods: Numerous recent publications involving the PE molecular mechanism for targeted-mutagenesis, advantages, limitations, and applications of the approach in different biomedicine fields were reviewed. Results: From the literature, it appears that PE neither relies on DSB nor needs HDR with exogenous donor DNA templates, which shows the clinical potential of PEs in correcting a broad range of mutations for genetic diseases. Four generations of PE mechanisms have been developed, reaching higher efficiency from one generation to the next one. However, reviewed studies support that PE also introduces new challenges such as unwanted mutations mediated by the double nicking strategy required for the PE3's efficiency, the selection of the optimal combination of PBS and RT templates, and the limitation of large DNA insertions that conventional CRISPR-Cas9 is capable of. Conclusion: The reviewed literature demonstrate that genome editing-based PE is a promising technology aiming at decreasing the common undesirable effects associated with conventional genome editing approaches such as CRISPR-Cas9 or BE. Even though progress has been made to improve the efficiency of the genome editing by the PE ribonucleo-protein complex, further research is required to optimize PE tools and maximize its efficiency.https://www.liebertpub.com/doi/full/10.1089/REGEN.2021.0016Prime EditingCRISPR-Cas9site-specific mutagenesistransgenesis |
| spellingShingle | Adriana Ochoa-Sanchez Gabriela Perez-Sanchez A. Marianna Torres-Ledesma Juan Pablo R. Valdez Gabriel Rinaldi B?rbara B. Moguel B?rbara B. Moguel Christian Molina-Aguilar Christian Molina-Aguilar Prime Editing, a Novel Genome-Editing Tool That May Surpass Conventional CRISPR-Cas9 Re:GEN Open Prime Editing CRISPR-Cas9 site-specific mutagenesis transgenesis |
| title | Prime Editing, a Novel Genome-Editing Tool That May Surpass Conventional CRISPR-Cas9 |
| title_full | Prime Editing, a Novel Genome-Editing Tool That May Surpass Conventional CRISPR-Cas9 |
| title_fullStr | Prime Editing, a Novel Genome-Editing Tool That May Surpass Conventional CRISPR-Cas9 |
| title_full_unstemmed | Prime Editing, a Novel Genome-Editing Tool That May Surpass Conventional CRISPR-Cas9 |
| title_short | Prime Editing, a Novel Genome-Editing Tool That May Surpass Conventional CRISPR-Cas9 |
| title_sort | prime editing a novel genome editing tool that may surpass conventional crispr cas9 |
| topic | Prime Editing CRISPR-Cas9 site-specific mutagenesis transgenesis |
| url | https://www.liebertpub.com/doi/full/10.1089/REGEN.2021.0016 |
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