{"title":"CRISPR/Cas9编辑引起的非预期大靶基因修饰的检测和定量","authors":"So Hyun Park, Mingming Cao, Gang Bao","doi":"10.1016/j.cobme.2023.100478","DOIUrl":null,"url":null,"abstract":"<div><p>CRISPR/Cas9 based gene editing typically functions by creating a DNA double-strand break (DSB) at the intended target locus in a cell. Recent reports showed the occurrence of unintended on-target large gene modifications by CRISPR/Cas9-induced DSB, including large deletions, insertions, and chromosomal rearrangements, in addition to small insertions and deletions. These on-target large gene modifications can have high frequencies, undetectable by standard short-range PCR based assays, leading to data misinterpretation, reduced efficacy, and potential safety concerns in therapeutic gene editing. Here, we summarize the recent advances in analyzing large on-target gene editing outcomes and their implications to clinical application, and discuss opportunities for future improvements.</p></div>","PeriodicalId":36748,"journal":{"name":"Current Opinion in Biomedical Engineering","volume":null,"pages":null},"PeriodicalIF":4.7000,"publicationDate":"2023-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"2","resultStr":"{\"title\":\"Detection and quantification of unintended large on-target gene modifications due to CRISPR/Cas9 editing\",\"authors\":\"So Hyun Park, Mingming Cao, Gang Bao\",\"doi\":\"10.1016/j.cobme.2023.100478\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>CRISPR/Cas9 based gene editing typically functions by creating a DNA double-strand break (DSB) at the intended target locus in a cell. Recent reports showed the occurrence of unintended on-target large gene modifications by CRISPR/Cas9-induced DSB, including large deletions, insertions, and chromosomal rearrangements, in addition to small insertions and deletions. These on-target large gene modifications can have high frequencies, undetectable by standard short-range PCR based assays, leading to data misinterpretation, reduced efficacy, and potential safety concerns in therapeutic gene editing. Here, we summarize the recent advances in analyzing large on-target gene editing outcomes and their implications to clinical application, and discuss opportunities for future improvements.</p></div>\",\"PeriodicalId\":36748,\"journal\":{\"name\":\"Current Opinion in Biomedical Engineering\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.7000,\"publicationDate\":\"2023-06-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"2\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Current Opinion in Biomedical Engineering\",\"FirstCategoryId\":\"5\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S246845112300034X\",\"RegionNum\":3,\"RegionCategory\":\"工程技术\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"ENGINEERING, BIOMEDICAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current Opinion in Biomedical Engineering","FirstCategoryId":"5","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S246845112300034X","RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ENGINEERING, BIOMEDICAL","Score":null,"Total":0}
Detection and quantification of unintended large on-target gene modifications due to CRISPR/Cas9 editing
CRISPR/Cas9 based gene editing typically functions by creating a DNA double-strand break (DSB) at the intended target locus in a cell. Recent reports showed the occurrence of unintended on-target large gene modifications by CRISPR/Cas9-induced DSB, including large deletions, insertions, and chromosomal rearrangements, in addition to small insertions and deletions. These on-target large gene modifications can have high frequencies, undetectable by standard short-range PCR based assays, leading to data misinterpretation, reduced efficacy, and potential safety concerns in therapeutic gene editing. Here, we summarize the recent advances in analyzing large on-target gene editing outcomes and their implications to clinical application, and discuss opportunities for future improvements.