秒速赛车控制器

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楊輝:探索基因編輯技術,致力于罕見病治療
發布時間: 2019-12-09     來源: 藥明康德

JIYINBIANJIKEYISHUOSHI21SHIJIZUIWEIDADEKEXUECHENGJIUZHIYI。DISANDAICRISPR/Cas9JIYINBIANJIJISHUZAIDNABIANJIFANGMIANDEJIANJIEXINGHEGAOXIAOXINGSHIQIXUNSUCHENGWEIDANGQIANSHENGMINGKEXUEZUIWEIZHISHOUKEREDELINGYUZHIYI,DANQITUOBAXIAOYINGYESHIYIZHIJIXUGONGKEDENANTI,ZHIYUEZHUQIZAILINCHUANGSHANGDEJINYIBUYINGYONG。WEICI,JIANLIGENGWEIGAOXIAO、ANQUANDEJIYINBIANJIGONGJU,KAIFAGENGWEILINGMINDETUOBAJIANCEJISHU,CHENGWEILEQUANQIUYANJIUDEREDIAN。

秒速赛车控制器ZHONGGUOKEXUEYUANSHENJINGKEXUEYANJIUSUOYANJIUYUAN、LINGCHANGLEIJIBINGMOXINGYANJIUZUZUCHANGYANGHUIDUONIANLAIZHUANGONGJIYINBIANJIJISHUDEYANJIU,DUIJIYINBIANJIZHONGDETUOBAANQUANXINGJIANCEYIJISHIYONGGAIJISHUJIANLIDONGWUMOXINGHETANSUOJIYINZHILIAOFANGMIANHUODELEYIXILIEYUANCHUANGXINGCHENGGUO。YANGHUIJIANLIDEGENGGAOJINGDUDEDANJIANJIBIANJIGONGJU,WEIDANJIANJIBIANJIJISHUJINRULINCHUANGZHILIAOTIGONGLEZHONGYAODEJICHU。ZAIJINRIGONGBUDE2019NIANDISHISANJIEYAOMINGKANGDESHENGMINGHUAXUEYANJIUJIANGZHONG,YANGHUIPINGJIEGAIJINJIYINBIANJIJISHUHETUOBAANQUANJIANCESHOUDUAN,RONGYINGJIECHUCHENGJIUJIANG。

▲ZHONGGUOKEXUEYUANSHENJINGKEXUEYANJIUSUOYANJIUYUAN、LINGCHANGLEIJIBINGMOXINGYANJIUZUZUCHANGYANGHUI

結緣基因編輯技術

秒速赛车控制器SHUOQIYANGHUIYUJIYINBIANJIDEXIEHOUYAOZHUISUDAO2012NIAN。NEIYINIANYANGHUILAIDAOMIT Whitehead YANJIUSUOCONGSHIBOSHIHOUYANJIUGONGZUO,SHICONGRudolf JaenischJIAOSHOU,HOUZHESHIGOUJIANDIYIZHIZHUANJIYINXIAOSHUDEXUESHUTAIDOU。BUJIU,GEBIDEBroadYANJIUSUO,CRISPRXIANQUZHANGFENGTUANDUISHOUCIZHENGSHILEJIANG CRISPR XITONGYONGYUBURUDONGWUXIBAODEJIYINBIANJI。

秒速赛车控制器LUNWENFABIAOHOU,YANGHUIYUZIJIDANGSHIDETONGMEN,XIANZAIZHONGKEYUANDONGWUSUORENZHIDEWANGHAOYIBOSHIXUNSUZHANKAICRISPR/Cas9ZAIXIAOSHUMOXINGSHANGDEYINGYONGYANJIU。DUANDUANBANNIANSHIJIAN,LIANGRENJIUZHENGMINGLECRISRP/Cas9KEYIGAOXIAOHUODEDUOZHONGJIYINXIUSHIDONGWU,BAOKUOJIYINQIAOCHUXIAOSHU、JIYINQIAORUXIAOSHU、JINGQUEXIUFUDEXIAOSHU,ZHIJINRENGBEIZUOWEIQUANQIUBIAOZHUNDEJIYINXIUSHIFANGFA。

秒速赛车控制器HUIGUOHOU,YANGHUIBOSHILAIDAOZHONGKEYUANSHENJINGSUODANRENLINGCHANGLEIJIBINGMOXINGYANJIUZUFUZEREN,JIXUCONGSHIJIYINBIANJIDONGWUMOXING,YOUQISHILINGCHANGLEIMOXINGDEXIANGGUANYANJIU。DUIYUZHEYIXUANZE,YANGHUIBIAOSHI,FEIRENLINGCHANGLEISHIZUIJIEJINRENLEIDEMOSHIDONGWU,DUIYANJIURENLEIJIBING,TEBIESHINAOJIBINGLAISHUOJUYOUDUYOUDEYOUSHI。RANER,JIUZAISHIYANSHICHENGLIZAOQI,YIGEWUXINCHALIUDESHIYANFAXIAN,GAIBIANLESHIYANSHIDEYANJIUFANGXIANG。

秒速赛车控制器2017NIAN,YANGHUIYANJIUZUHEHEZUOZHEFAXIANCRISRP/Cas9BUJINJINKEYIBIANJIDANGEJIYIN,HUANKEYIQIAOCHURANSETI,WEITANGSHIZONGHEZHENGZHILIAOTIGONGLEXINSILU。YANGHUIBENYIWEIGUSHIDAOCIWEIZHI,QUEYIWAIDISHOUDAOXUDUOTANGSHIHUANZHEJIASHUDELAIXINHEYOUJIAN,HUOGULITAMENJIXUKAIZHANYANJIU,HUOXUNWENTAMENDEFANGFAHESHISHANGLINCHUANG。“ZHEXIEJIASHUDEFANKUIGEIWOCHUDONGFEICHANGDA,RANGWODIYICIZHENZHENGYISHIDAO,ZIJIZUODEJICHUKEYANYULINCHUANGYINGYONGJINYOUYIBUZHIYAO。”YOUCI,YANGHUIZHUANERGUANZHUJIYINBIANJIJISHUDELINCHUANGYINGYONG,TEBIESHIHANJIANBINGHUANZHEQUNTI。

發現單堿基編輯工具存在嚴重脫靶效應

秒速赛车控制器RENHEXINDEJISHU、XINDEFANGFADELUODIZHUANHUADOUXUYAOJINGGUOYANJINDEANQUANXINGPINGGU。HERUHUORUTUDEJIYINBIANJIJISHUYANJIUXIANGBI,MUQIANQUANQIUZHIYOULIANGKUANJIYINBIANJIYAOWUHUOPILINCHUANGSHIYAN,JIUQIYUANYINZAIYUJIYINBIANJIDETUOBAXIAOYING。SUOWEI“TUOBAXIAOYING”,JIANDANSHUOJIUSHIMEIYOUBIANJIDAOXIANGYAOBIANJIDEMUBIAOJIYIN,FANERQUBIANJILEQITAJIYIN。

秒速赛车控制器ZAIYANGHUIYANLI,TUOBAWENTIXUYAOCONGLIANGGEFANGMIANJINXINGKAOLV,YISHIJIYINBIANJIJISHUBENSHENNENGFOUGENGHAODIBIMIANTUOBA,ERSHIDANGXINDEJISHUDANSHENG,NENGFOUJIANLIGENGHAODEJIANCEFANGFAZHENGMINGQIANQUANXING?

秒速赛车控制器JINNIAN3YUE,YANGHUITUANDUIYUHEZUOZHEZAI《Science》SHANGFABIAOLEWENZHANG,YANJIUJIANLILEYIZHONGBEIMINGMINGWEIGOTI(Genome-wide Off-target analysis by Two-cell embryo Injection)DEXINXINGTUOBAJIANCEJISHU,BINGSHIYONGGAIJISHUFAXIAN:JINNIANLAIXINGQIDEDANJIANJIBIANJIJISHUYOUKENENGDAOZHIDALIANGWUFAYUCEDETUOBA,YINERCUNZAIYANZHONGDEANQUANFENGXIAN。

▲YANGHUITUANDUIYUHEZUOZHEZAI《Science》SHANGFABU“GOTI”XINXINGTUOBAJIANCEJISHU

秒速赛车控制器GOTIKEYIZAIBUJIEZHUYURENHETUOBAWEIDIANYUCEJISHUDEQINGKUANGXIA,FAXIANZHIQIANWUFAFAXIANDEWANQUANSUIJIDETUOBAWEIDIAN,CONGERTISHENGTUOBAJIANCEDEMINGANXING。SHIYANSHEJIJINGMIAOZAIYU,YANJIUZHESHIZAILIANGQUNYICHUANBEIJINGWANQUANXIANGTONGDEXIBAOSHANGJINXINGSHIYAN,XIAOCHULEYANGBENZHIJIANDEFEITEYIGANRAO,YOUCIKEYIZUIDACHENGDUQUEDINGYICIJIYINBIANJIGAIBIANLEDUOSHAOBENBUYINGGAIBEIGAIBIANDEJIYIN,YEJIUSHI“TUOBA”DECHENGDU。 

秒速赛车控制器SHIJIANZHONG,YANGHUITUANDUIYONGGOTIJIANYANLEDUOZHONGJIYINBIANJIJISHU,QIZHONGJIUBAOKUOCENGBEIRENWEIBICRISPR/Cas9GENGJINGZHUN、GENGANQUANDEDANJIANJIBIANJIJISHU。DANYANGHUITUANDUIFAXIAN,DANJIANJIBIANJIJISHUKEDAOZHIDALIANGWUFAYUCEDETUOBA,QIEDADUOCHUXIANZAICHUANTONGTUOBAYUCERENWEIBUTAIKENENGTUOBADEWEIDIAN,BUFENTUOBAWEIDIANSHENZHICHUXIANZAILEYIAIJIYINSHANG。ZHEXIANGYANJIUFAXIANFABIAOHOU,GUOWAILIANGJIAGONGSILIJIJIAOTINGZHENGZAITUIXIANGLINCHUANGDELIANGGEXIANGMU,ZHONGXINGUIHUAZIJIDECHANPINLUXIAN。

建立更精準的單堿基編輯工具

ZAIZHENGMINGDANJIANJIJIYINBIANJIKENENGDAOZHIDALIANGWUFAYUCEDEDNATUOBAXIAOYINGDEJICHUSHANG,YANGHUITUANDUIHEHEZUOZHEJINYIBUJIANGTUOBADEJIANCEFANWEIKUOZHANDAORNASHUIPING,SHOUCIZHENGMINGCHANGYONGDEJIZHONGDANJIANJIBIANJIJISHUYECUNZAIDALIANGDERNATUOBA,QIEJUYOUJIAOQIANGDEZHIAIFENGXIAN。

秒速赛车控制器RUCIYILAI,DANJIANJIBIANJIJISHUSHIFOUYINGGAIBEI“DARULENGGONG”NI?SHISHIBINGFEIRUCI。WOMENLAIKANZHEJIGESHUJU:QUANQIUYUE7QIANZHONGHANJIANBING,90%DEHANJIANBINGWUYAOKEZHI,80%DEHANJIANBINGSHIDANJIANJITUBIANDAOZHI。YINCI,DANJIANJIBIANJIJISHUZAIZHILIAODANJIYINYICHUANBINGZHONGBEIJIYUHOUWANG。RUGUONENGJIEJUETUOBAWENTI,DANJIANJIJIYINBIANJIJISHURENGYOUJUDADEYINGYONGJIAZHI。

▲《Nature》FABUYANGHUITUANDUIYOUHUAHOUDEGAOBAOZHENDANJIANJIJIYINBIANJIJISHU

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ZHEYIYANJIUFABIAOZAIJINNIAN6YUE《Nature》ZAZHISHANG,PINGSHENZHUANJIAGEICHULEGAODUPINGJIA,RENWEI“ZHESHIYIXIANGZUODEHENHAODEYANJIU,BINGYOUSHIDANGDEDUIZHAOKONGZHI。TIGONGDEJIANGDIRNATUOBADEDANJIANJIBIANJIQI,DUIJIYINBIANJILINGYUJUYOUZHONGYAOJIAZHI。”

劍指臨床轉化

JINNIANLAI,YANGHUIGONGZUODEZHONGDIANJIANGQITUPOXINGDEJICHUYANJIUXIANGLINCHUANGZHUANHUA。YANGHUIJIESHAO,TAMENZHENGZAICHANGSHIYONGJIYINBIANJISHOUDUANZHILIAOJISUIXINGJIYINGYANGBULIANG(SMA)HESHIWANGMOHUANGBANBINGBIANDENGJIBING。

秒速赛车控制器YISMAJULI。SMASHIYIZHONGYOUJIYINQUEXIANSUODAOZHIDECHANGRANSETIYINXINGYICHUANBING,SHILIANGSUIYIXIAYINGYOUERDETOUHAOYICHUANBINGSHASHOU,SHUYUHANJIANBINGLIJIWEIYANZHONGDEYIZHONG。SMAZAI“HANJIANBING”ZHONGXIANGDUICHANGJIAN,QIZHIBINGJIYINDEXIEDAILVFEICHANGGAO,MEI50GEPUTONGRENZHONGJIUYOUYIGESHIXIEDAIZHE。RUGUOFUQISHUANGFANGTONGWEIXIEDAIZHE,ZEMEIYITAISHENGHUANERDEGAILVWEI25%。MUQIAN,QUANQIUSUIYIYOULIANGKUANZHENDUIGAIJIBINGDEYAOWUSHANGSHI,DANGAOANGDEZHILIAOFEIYONGFEIYIBANZHONGGUOJIATINGNENGGOUCHENGSHOU。

TANQIZHEYIJIBINGZHILIAOLINGYU,YANGHUITOULU,TAMENZAISHIYANSHIZHONGYIJINGCHENGGONGDILIYONGJIYINBIANJIJISHU,ZAIXIAOSHUDONGWUMOXINGSHANGSHIXIANLEDUISMAJIBINGJIYINDEXIUFU。JINGGUOCHIXUYINIANYISHANGDEGUANCHAFAXIAN,JIYINXIUFUDEXIAOSHUFEICHANGJIANKANG。JIEXIALAIJIUSHIKAOLVRUHEJIANGZHETAOJISHUTUIXIANGLINCHUANG,MANZULINCHUANGXUQIU。

秒速赛车控制器DANGBEIWENJISHUSHINIANKEYANLICHENGZHONGNAJIANSHIZUIZHIDEZIHAOSHI,YANGHUIDADAO:“WOZUIDADEMENGXIANGSHINENGGOUZUOCHENGYIGEYAO,RANHOUJIANGZHEGEYAOQINSHOUJIAODAOHUANZHESHOUZHONG,RANGJIBINGBEIZHIYU,RANGHUANZHEZHONGXINHUODEJIANKANG。WOXIANGZHEHUIDAIGEIZIJIGENGDADEGUANGRONG。”RUJIN,YANGHUIHUANSHIYIJIACHUCHUANGGONGSIDECHUANGSHIRENJIANSHOUXIKEXUEJIA。GENJUZILIAOXIANSHI,GAIGONGSISHIYIJIAJIYUJIYINZHILIAOYAOWUYANFADEZHUANHUAXINGSHENGWUKEJIQIYE,ZHILIYURENLEIHANJIANYICHUANJIBINGXINXINGZHILIAOJISHUJIYAOWUDEYANFA。