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病毒检测中的福尔摩斯—基于CRISPR的SHERLOCK系统

来源:中国知识产权网     发布时间:2020-02-25     点击量:
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  前言

  DUIYULIUXINGXINGCHUANRANJIBING,TEBIESHIJUYOUYIDINGQIANFUSHIQI(YOUQISHIWUZHENGZHUANGHUOQINGZHENGZHUANGQIANFUSHIQI)DEBINGDUGANRAN,DUIHUANBINGRENYUANDEQUEZHENDOUFEICHANGZHONGYAO。WULUNSHI2003NIANDEFEIDIANHAISHIWOMENXIANZAIZHENGZAIZAOSHOUDEXINXINGGUANZHUANGBINGDU(COVID-19)YIQING,RUGUONENGZAIGANRANCHUQIHUOZHEQINGZHENGSHIQIJIKETONGGUOJIANCESHOUDUANJINXINGQUEZHEN,ZHIYUJILVJIYUHOUQINGKUANGDOUHUIDADATIGAO。

  现有病毒检测试剂盒分类

  1.胶体金免疫层析法(检测抗原)

球探足球比分直播  MEINIANDONGTIAN,HENDUORENDOUHUIBUKEBIMIANDIGANRANSHANGJIAXINGHUOYIXINGLIUGAN。QIANWANGYIYUANHOUYISHENGHUITONGGUOBIYANSHIZIQUYANGBINGKUAISUQUEZHENBINGHUANSHIFOULIHUANGAIZHONGBINGDUXINGGANMAO,ERQINENGKUAISUPANDUANDEYIJUJIUSHIJIALIU/YILIUKANGYUANKUAISUJIANCESHIJIHE(JIAOTIJINFA),ZHEIZHONGSHIJIHEKEYIZAIJIAODUANSHIJIANNEIJIYUYISHENGQUEDINGJIEGUO,ERQIECAOZUOFEICHANGJIANBIAN。

  MIANYIJIAOTIJINJISHU(Immune Colloidal Gold, ICG)SHIXIANYOUJIAOWEICHENGSHUDEGUXIANGBIAOJIMIANYICEDINGJISHU,GAIJISHUYIJIAOTIJINWEIBIAOJIWU,LIYONGTEYIXINGKANGYUANKANGTIFANYING,TONGGUODAIYANSEDEJIAOTIJINKELILAIFANGDAMIANYIFANYINGXITONG,CAOZUOJIANDAN,BIAOJIMINGXIAN,CONGERZHIGUANJIANCEDAICEYANGPINZHONGDEKANGYUANHUOKANGTI,ZUIKUAIKEYIZAI15FENZHONGNEIHUODEJIANCEJIEGUO。

  2.RT-PCR方法(检测核酸)

球探足球比分直播  KANGTIDEZHIBEISHIXUYAOYIDINGSHIJIANTONGGUOYANJIUHESHIYANLAIHUODE,YEXUYAODUOCIDEZHONGFUYIQUEBAOJIANCEDEZHUNQUEDU。SUOYIZAICICIXINXINGGUANZHUANGBINGDUZHONGXIANCAIQUYINGGUANGRT-PCR(SHISHIYINGGUANGFANZHUANLUJUHEMEILIANSHIFANYING)JINXINGJIANCE。

  TONGGUOBIYANSHIZIQUYANG,TIQUBINGDUJIYINZURNA,TONGGUOFANZHUANLUXINGCHENGcDNA,SHIYONGSHEJIDETEYIXINGYINWU,YICONGDNAZUOWEIMOBANKUOZENGBINGYUANTIHESUANXULIE。JIEGUOKETONGGUOJIEHEZAICHANWUSHANGDEYINGGUANGRANLIAOXINHAOQIANGRUOJINXINGSHISHIJIANCE。

球探足球比分直播  YOUYUCOVID-2019SHIYIZHONGXINXINGGUANZHUANGBINGDU,ZAIHUOQUTADEQUANJIYINZUXULIEHOU,WOMENJIUKEYITONGGUOBIDUIXUANQUQIZHONGDETEYIQUDUAN,SHEJIYINWU,JINXINGJIANCE。SUIRANZHEIZHONGFANGFAXUYAODESHIYANSHEJISHIJIANJIAODUAN,JILIQINGCHU,DANYOUYURT-PCRBENSHENDETEXING(JIAYANGXINGGAO、SHIYANJIEGUOBUWENDING),ZAIJIASHANGYINWUDEJIEHEXIAOLV、PCRCHENGXUYOUHUACHENGDUDENGJUNHUIDUIJIANCEJIEGUOCHANSHENGYINGXIANG。CHUCIYIWAI,CICIXINGUANBINGDUZHUYAOZAIFEIBUNONGDUJIAOGAO,ZAIYANHOUBUNONGDUKENENGJIAODI,ZHEIJIUDAOZHIBIYANSHIZIQUYANGHOUTIQUHENLIANGRNAJIAOWEIKUNNAN,ZHEIKENENGYESHIDUIHUANBINGRENYUANJINXINGHESUANJIANCESHIHUICHANSHENGYINXINGJIEGUODEYUANYIN。

  初显锋芒的SHERLOCK系统

  TIQIZHANGFENG,SHENGWUJIEDERENDOUBUHUIMOSHENG,ZUOWEIMASHENGLIGONGDAXUE/HAFOBroadYANJIUSUODEZHONGSHENJIAOSHOU,TASHIJIYINZUBIANJILINGYU(Genome Editing)DELINGJUNJIRENWUZHIYI,YONGYOUDUOJIANCRISPRZHUANLI,CENGJINGYUTONGYANGSHICRISPRLINGYUDEDIANJIRENWUJannifer DoudnaJIAOSHOU(JIAZHOUBOKELIFENXIAO)ZAICRISPRZHUANLIGUISHUSHANGYOUGUOFENZHENG。

  CRISPR/Cas系统有多种类型,其中Cas13尤为特殊,它是一类依赖于RNA靶向的RNA核酸酶,专一切割RNA,这一特性为RNA病毒的检测和治疗提供了便利。2017年,张峰在顶尖科研杂志SCIENCE上发表了《Nucleic acid detection with CRISPR-Cas13a/C2c2》这篇文章(),首次介绍了SHERLOCK(Specific High Sensitivity Enzymatic Reporter UnLOCKing)技术,并且申请了多篇专利对该系统及其在诊断和治疗上的应用进行保护,其原理如下图所示。

Figure 1. SHERLOCKJISHUYUANLI

  WEILEKANGJIXINGUANBINGDUYIQING,ZHANGFENGJIAOSHOUTONGSHIGONGBULESHERLOCKXITONGDECAOZUOZHINAN,BINGQIEZAICAOZUOZHINANZHONGSHEJILELIANGGEZHENDUIYUGUANZHUANGBINGDUDEXIANGDAORNAHEBAOGAORNA,XULIERUXIA:

  >S-crRNA_v1

  GAUUUAGACUACCCCAAAAACGAAGGGGACUAAAACGCAGCACCAGCUGUCCAACCUGAAGAAG

  >Orf1ab-crRNA

  GAUUUAGACUACCCCAAAAACGAAGGGGACUAAAACCCAACCUCUUCUGUAAUUUUUAAACUAU

  >Lateral-Flow-Reporter

  5‘-/56FAM/mArArUrGrGrCmAmArArUrGrGrCmA/3Bio/-3’

  SHERLOCK系统相关专利情况

球探足球比分直播  S-crRNAHEOfr1ab-crRNASHIFENBIEZHIXIANGCOVID-19DESDANBAIHEOrf1abDANBAI,Lateral-Flow-ReporterZESHIQIEGEHOUKEFACHUYINGGUANGDEBAOGAORNA。WEILEQUEBAOXIANGDAORNAKETEYIHEBAXIANGDAIJIANCEBINGDUXIANGJIEHE,BUFENXULIESHIXUYAOHEBADIANHUBU,TONGGUOJIANSUOWOMENKEYIFAXIANRUTU2SUOSHI,XIANGDAOXULIEDEQIAN28bpJUNHECICICOVID-2019XIANGGUANXULIE100%PIPEI。

球探足球比分直播Figure 2. XIANGDAORNATONGCOVID-19DEPIPEIQINGKUANG

球探足球比分直播  JIANGZHEISANTIAOZHONGYAOXULIETONGSHIZAIZHUANLIXULIEDESHUJUKUZHONGJINXINGBIDUI,FAXIANSANTIAOXULIEZAIZHUANLILIMIANDEFENBUZHUANGKUANGRUTU3SUOSHI:

Figure 3. 各条序列在专利中的分布情况 

  KEJIANGONGYOU20PIANXIANGGUANZHUANLITONGSHIBAOHANZHEISANTIAOXULIE,DIANJIJINRUHOUCHAKANZHUANLIXINXI,SUOYOUZHUANLIDEQUANLISUOYOURENJUNWEIZHANGFENGJIAOSHOUJIQISUOZAIDEBroadYANJIUSUO,QIEJUNZHUANZHUYUJIYUCRISPRDEZHENDUAN(TU4).

球探足球比分直播Figure 4. XULIEJIANSUOHUODEDEZHUANLIQINGKUANG

  GENJUBIDUI,KEJIANZAIWO2019051318,WO2019126577HEWO2019071051ZHEISANPIANZHUANLILIBAOGAORNAJUNWEI100%PIPEI。YIWO2019071051WEILI,GAIXULIEWEIYUZHUANLISEQ ID 451CHU,CONGZHUANLIYUANWENDEBIAOGELIKEYIKANDAOXIANGGUANXULIE(TU5).

Figure 5. Lateral flow reporter RNAZAIZHUANLIZHONGSUOCHUWEIZHI

球探足球比分直播  ERS-crRNAHEOrf1ab-crRNADEXIANGSIXULIEYEZAIZHUANLIZHONGCHUXIAN,WEIYUCESHIDEcrRNADELIEBIAOZHONG(TU6)

Figure 6. S-crRNAHEOrf1ab-crRNADEXIANGSIXULIEZAIZHUANLIZHONGSUOCHUWEIZHI

  JIANG20PIANZHUANLIDAORUDAOPatbaseZHONGJINXINGFENXI,ZHEI20PIANZHUANLIFENSHUYU6GEZHUANLIJIAZU,JUNWEIPCTZHUANLI,CHUYUJINRUGUOJIAJIEDUAN,RUTU7SUOSHIZHUYAOBUJUZAIMEIGUO、AODALIYA、JIANADAHEHANGUO,XIANJINYOULIANGJIANZHUANLIYIZAIMEIGUOSHOUQUAN(US20180917546HEUS20180917549)。

Figure 7. SHERLOCKJIANCEZHUANLISHENQINGDEGUOJIABUJUZHUANGKUANGHESHOUQUANZHUANLI

  ZHEI6GEZHUANLIJIAZUCONGHESUANJIANCEXITONGJICRISPRXITONG(BAOKUOQIXIAODANBAI、XIANGDAOXULIEYIJIJIYURNADEGOUJIANTI)、QIDUIBINGDUDEJIANCEFANGFA、DUOZHONGXINHAOFANGDAJILIANDECRISPRXIAOYINGDANBAI、HENGXIANGLIUDONGDEZHENDUANZHUANGZHI、KEJIANCEDUOTIAOBADIANXULIEDECRISPRXITONGDENGDUOFANGMIANDUIGAIJISHUJINXINGLEXIANGGUANBAOHU。CHUQUZHENDUANFANGMIANYONGTU,ZHUANLIWO2019010422HAIBAOHULECRISPRXITONGDUIYUKANGBINGDUZHILIAODEZUOYONG。SUIRANXIANGJIAOYUCHUANTONGDEreal-time PCRJISHULAISHUO,SHERLOCKJISHUJUYOULINGMINDUGAO、JIEGUOZHIGUAN、ZHUNQUEDUGAO、JIAGEHEJIANCESHIJIANDIDENGYOUSHI,DANZHENZHENGYINGYONGDAOLINCHUANGJIANCESHANGHAIXUYAOJINXINGDALIANGDESHIYAN,ERZHANGFENGJIAOSHOUYEMINGQUEZAIProtocolSHANGZHUMINGGAISHIYANLIUCHENGBUNENGYONGYULINCHUANGMUDE。WULUNZENYANG,SHERLOCKXITONGDECUNZAIWEIWOMENNENGGOUJINKUAIJIANCECHUHUANBINGRENYUAN,TEBIESHIWUZHENGZHUANGGANRANZHETIGONGLECANKAO。

  数据库使用

  为了让更多的科研人员拥有更多工具和数据库对新冠病毒情况进行分析,我们特意为相关科研和知识产权人员开放全球专利及化学结构检索数据库Patbase和生物序列检索数据库GenomeQuest的免费试用账号,诸位可通过邮件联系后获取相关账号。

  WOMENXIWANGYOUGENGDUODEKEYANRENYUANNENGGOUJINKUAIHUODEZUIWEIXIANGGUANDESHUJU,WEIDAYINGZHEICHANGZHAN“YI”ZHENGQUDAOGENGDUODESHIJIAN,HUANYINGDAJIAJIUXIANGGUANYITIJINXINGTANTAO。

  联系邮箱:zhaolina@cnipr.com(请注明您的单位邮箱、姓名和所在单位)

  PatbaseHUAXUEJIEGOUJIANSUOJIEMIAN:

球探足球比分直播  GenomeQuestZHUANLIJIFEIZHUANLIXULIEJIANSUOJIEMIAN(BAOHANZHUANMENDE2019-nCovXULIEKU):

  为了更多感兴趣的读者了解SHERLOCK系统,我们将SHERLOCK的实验流程、基于CRISPR的病毒检测系统专利(WO2018170340)及专利内所含有的全部序列(核酸及蛋白序列,FASTA格式)附于文章后,供大家参考。

XIANGSUOYOUYIXIANKANGYIYONGSHIZHIJING!

球探足球比分直播SHIBIEERWEIMACHAKANHUAHEWUJIEGOUSHIBIAODAN

球探足球比分直播LIANXIYOUXIANG:zhaolina@cnipr.com

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