CRISPR prime editing for unconstrained correction of oncogenic KRAS variants
Abstract KRAS is the most commonly mutated RAS family gene and is a primary cause of the occurrence of several types of cancer. However, KRAS mutations have several unique and diverse molecular identities, making it difficult to find specific treatments. Here, we developed universal pegRNAs which ca...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-06-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-023-05052-1 |
| _version_ | 1797789620501479424 |
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| author | Gayoung Jang Jiyeon Kweon Yongsub Kim |
| author_facet | Gayoung Jang Jiyeon Kweon Yongsub Kim |
| author_sort | Gayoung Jang |
| collection | DOAJ |
| description | Abstract KRAS is the most commonly mutated RAS family gene and is a primary cause of the occurrence of several types of cancer. However, KRAS mutations have several unique and diverse molecular identities, making it difficult to find specific treatments. Here, we developed universal pegRNAs which can correct all types of G12 and G13 oncogenic KRAS mutations with CRISPR-mediated prime editors (PEs). The universal pegRNA successfully corrected 12 types of KRAS mutations, accounting for 94% of all known KRAS mutations, by up to 54.8% correction frequency in HEK293T/17 cells. We also applied the universal pegRNA to correct endogenous KRAS mutations in human cancer cells and found that G13D KRAS mutation was successfully corrected to wild-type KRAS sequences with up to 40.6% correction frequency without indel mutations. We propose prime editing with the universal pegRNA as a ‘one–to–many’ potential therapeutic strategy for KRAS oncogene variants. |
| first_indexed | 2024-03-13T01:53:16Z |
| format | Article |
| id | doaj.art-2faf4a85fb8f469a8e2220d1d90e7ad6 |
| institution | Directory Open Access Journal |
| issn | 2399-3642 |
| language | English |
| last_indexed | 2024-03-13T01:53:16Z |
| publishDate | 2023-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj.art-2faf4a85fb8f469a8e2220d1d90e7ad62023-07-02T11:23:18ZengNature PortfolioCommunications Biology2399-36422023-06-01611710.1038/s42003-023-05052-1CRISPR prime editing for unconstrained correction of oncogenic KRAS variantsGayoung Jang0Jiyeon Kweon1Yongsub Kim2Department of Cell and Genetic Engineering, Asan Medical Institute of Convergence Science and Technology, Asan Medical Center, University of Ulsan College of MedicineDepartment of Cell and Genetic Engineering, Asan Medical Institute of Convergence Science and Technology, Asan Medical Center, University of Ulsan College of MedicineDepartment of Cell and Genetic Engineering, Asan Medical Institute of Convergence Science and Technology, Asan Medical Center, University of Ulsan College of MedicineAbstract KRAS is the most commonly mutated RAS family gene and is a primary cause of the occurrence of several types of cancer. However, KRAS mutations have several unique and diverse molecular identities, making it difficult to find specific treatments. Here, we developed universal pegRNAs which can correct all types of G12 and G13 oncogenic KRAS mutations with CRISPR-mediated prime editors (PEs). The universal pegRNA successfully corrected 12 types of KRAS mutations, accounting for 94% of all known KRAS mutations, by up to 54.8% correction frequency in HEK293T/17 cells. We also applied the universal pegRNA to correct endogenous KRAS mutations in human cancer cells and found that G13D KRAS mutation was successfully corrected to wild-type KRAS sequences with up to 40.6% correction frequency without indel mutations. We propose prime editing with the universal pegRNA as a ‘one–to–many’ potential therapeutic strategy for KRAS oncogene variants.https://doi.org/10.1038/s42003-023-05052-1 |
| spellingShingle | Gayoung Jang Jiyeon Kweon Yongsub Kim CRISPR prime editing for unconstrained correction of oncogenic KRAS variants Communications Biology |
| title | CRISPR prime editing for unconstrained correction of oncogenic KRAS variants |
| title_full | CRISPR prime editing for unconstrained correction of oncogenic KRAS variants |
| title_fullStr | CRISPR prime editing for unconstrained correction of oncogenic KRAS variants |
| title_full_unstemmed | CRISPR prime editing for unconstrained correction of oncogenic KRAS variants |
| title_short | CRISPR prime editing for unconstrained correction of oncogenic KRAS variants |
| title_sort | crispr prime editing for unconstrained correction of oncogenic kras variants |
| url | https://doi.org/10.1038/s42003-023-05052-1 |
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