Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 허준호 | - |
dc.date.accessioned | 2022-05-11T07:21:38Z | - |
dc.date.available | 2022-05-11T07:21:38Z | - |
dc.date.issued | 2020-09 | - |
dc.identifier.citation | NUCLEIC ACIDS RESEARCH, v. 48, no. 15, page. 8601-8616 | en_US |
dc.identifier.issn | 0305-1048 | - |
dc.identifier.issn | 1362-4962 | - |
dc.identifier.uri | https://academic.oup.com/nar/article/48/15/8601/5873807?login=true | - |
dc.identifier.uri | https://repository.hanyang.ac.kr/handle/20.500.11754/170763 | - |
dc.description.abstract | The CRISPR-Cas9 system is widely used for target-specific genome engineering. CRISPR-Cas12a (Cpf1) is one of the CRISPR effectors that controls target genes by recognizing thymine-rich protospacer adjacent motif (PAM) sequences. Cas12a has a higher sensitivity to mismatches in the guide RNA than does Cas9; therefore, off-target sequence recognition and cleavage are lower. However, it tolerates mismatches in regions distant from the PAM sequence (TTTN or TTN) in the protospacer, and off-target cleavage issues may become more problematic when Cas12a activity is improved for therapeutic purposes. Therefore, we investigated off-target cleavage by Cas12a and modified the Cas12a (cr)RNA to address the off-target cleavage issue. We developed a CRISPR-Cas12a that can induce mutations in target DNA sequences in a highly specific and effective manner by partially substituting the (cr)RNA with DNA to change the energy potential of base pairing to the target DNA. A model to explain how chimeric (cr)RNA guided CRISPR-Cas12a and SpCas9 nickase effectively work in the intracellular genome is suggested. Chimeric guide-based CRISPR-Cas12a genome editing with reduced off-target cleavage, and the resultant, increased safety has potential for therapeutic applications in incurable diseases caused by genetic mutations. | en_US |
dc.description.sponsorship | National Research Foundation (NRF) funded by the Korean Ministry of Education, Science and Technology [NRF-2019R1C1C1006603]; Technology Innovation Program funded by the Ministry of Trade, Industry & Energy (MOTIE, Korea) [20009707]; Korea Research Institute of Bioscience & Biotechnology (KRIBB) Research Initiative Program [KGM4252021, KGM5382012, KGM1052021]. Funding for open access charge: KRIBBResearch Initiative Program [KGM4252021, KGM5382012, KGM1052021]. | en_US |
dc.language.iso | en | en_US |
dc.publisher | OXFORD UNIV PRESS | en_US |
dc.subject | STRUCTURAL BASIS | en_US |
dc.subject | CPF1 | en_US |
dc.subject | CAS9 | en_US |
dc.subject | ENDONUCLEASE | en_US |
dc.subject | COMPLEX | en_US |
dc.subject | MICE | en_US |
dc.title | Enhancement of target specificity of CRISPR-Cas12a by using a chimeric DNA-RNA guide | en_US |
dc.type | Article | en_US |
dc.relation.no | 15 | - |
dc.relation.volume | 48 | - |
dc.identifier.doi | 10.1093/nar/gkaa605 | - |
dc.relation.page | 8601-8616 | - |
dc.relation.journal | NUCLEIC ACIDS RESEARCH | - |
dc.contributor.googleauthor | Kim, Hanseop | - |
dc.contributor.googleauthor | Lee, Wi-jae | - |
dc.contributor.googleauthor | Oh, Yeounsun | - |
dc.contributor.googleauthor | Kang, Seung-Hun | - |
dc.contributor.googleauthor | Hur, Junho K. | - |
dc.contributor.googleauthor | Lee, Hyomin | - |
dc.contributor.googleauthor | Song, WooJeung | - |
dc.contributor.googleauthor | Lim, Kyung-Seob | - |
dc.contributor.googleauthor | Park, Young-Ho | - |
dc.contributor.googleauthor | Song, Bong-Seok | - |
dc.relation.code | 2020048779 | - |
dc.sector.campus | S | - |
dc.sector.daehak | COLLEGE OF MEDICINE[S] | - |
dc.sector.department | DEPARTMENT OF MEDICINE | - |
dc.identifier.pid | juhur | - |
dc.identifier.researcherID | ADK-0757-2022 | - |
dc.identifier.orcid | https://orcid.org/0000-0003-3794-1149 | - |
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