DNA Nicks Promote Efficient and Safe Targeted Gene Correction 英文参考文献.docVIP

下载本文档

7
0
约3.71万字
约 7页
2017-05-11 发布于上海
举报
版权申诉

DNA Nicks Promote Efficient and Safe Targeted Gene Correction 英文参考文献.doc

1、本文档共7页，可阅读全部内容。
2、原创力文档（book118）网站文档一经付费（服务费），不意味着购买了该文档的版权，仅供个人/单位学习、研究之用，不得用于商业用途，未经授权，严禁复制、发行、汇编、翻译或者网络传播等，侵权必究。
3、本站所有内容均由合作方或网友上传，本站不对文档的完整性、权威性及其观点立场正确性做任何保证或承诺！文档内容仅供研究参考，付费前请自行鉴别。如您付费，意味着您自己接受本站规则且自行承担风险，本站不退款、不进行额外附加服务；查看《如何避免下载的几个坑》。如果您已付费下载过本站文档，您可以点击这里二次下载。
4、如文档侵犯商业秘密、侵犯著作权、侵犯人身权等，请点击“版权申诉”（推荐），也可以打举报电话：400-050-0827(电话支持时间：9:00-18:30)。
5、该文档为VIP文档，如果想要下载，成为VIP会员后，下载免费。
6、成为VIP后，下载本文档将扣除1次下载权益。下载后，不支持退款、换文档。如有疑问请联系我们。
7、成为VIP后，您将拥有八大权益，权益包括：VIP文档下载权益、阅读免打扰、文档格式转换、高级专利检索、专属身份标志、高级客服、多端互通、版权登记。
8、VIP文档为合作方或网友上传，每下载1次，网站将根据用户上传文档的质量评分、类型等，对文档贡献者给予高额补贴、流量扶持。如果你也想贡献VIP文档。上传文档

DNA Nicks Promote Efficient and Safe Targeted Gene Correction 英文参考文献

DNANicksPromoteEfficientandSafeTargetedGene Correction LutherDavis1,3,NancyMaizels1,2,3 * 1DepartmentofImmunology,UniversityofWashingtonSchoolofMedicine,Seattle,Washington,UnitedStatesofAmerica,2DepartmentofBiochemistry,Universityof Washington School of Medicine, Seattle, Washington, United States of America, 3Northwest Genome Engineering Consortium, Seattle, Washington, United States of America Abstract Targeted gene correction employs a site-specific DNA lesion to promote homologous recombination that eliminates mutation in a disease gene of interest. The double-strand break typically used to initiate correction can also result in genomicinstabilityifdeleteriousrepairoccursratherthangenecorrection,possiblycompromisingthesafetyoftargeted gene correction. Here we show that single-strand breaks (nicks) and double-strand breaks both promote efficient gene correction. However, breaks promote high levels of inadvertent but heritable genomic alterations both locally and elsewhereinthegenome,whilenicksareaccompaniedbyessentiallynocollaterallocalmutagenesis,andthusprovidea safer approach to gene correction. Defining efficacy as the ratio of gene correction to local deletion, nicks initiate gene correctionwith70-foldgreaterefficacythandodouble-strandbreaks(29.066.0%and0.4260.03%,respectively).Thusnicks initiate efficient gene correction, with limited local mutagenesis. These results have clear therapeutic implications, and shouldinformfuturedesignofmeganucleasesfortargetedgenecorrection. Citation:DavisL,MaizelsN(2011)DNANicksPromoteEfficientandSafeTargetedGeneCorrection.PLoSONE6(9):e23981.doi:10.1371/journal.pone.0023981 Editor:MichaelLichten,NationalCancerInstitute,UnitedStatesofAmerica ReceivedJuly6,2011;AcceptedAugust1,2011;PublishedSeptember1,2011 Copyright: ? 2011 Davis, Maizels. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricteduse,distribution,andreproductioninanymedium,providedtheorigi