{"id":82611,"date":"2019-04-15T00:00:50","date_gmt":"2019-04-17T02:55:05","guid":{"rendered":"http:\/\/www.05921.net\/index.php\/82611\/"},"modified":"2019-04-17T10:55:11","modified_gmt":"2019-04-17T02:55:11","slug":"6a26f6930b","status":"publish","type":"post","link":"https:\/\/www.05921.net\/index.php\/82611\/","title":{"rendered":"\u300a\u81ea\u7136\u300b\u53cc\u91cd\u78c5\uff1a\u730e\u6740\u764c\u7ec6\u80de\u57fa\u56e0\u540d\u5355\u53d1\u5e03\uff01\u79d1\u5b66\u5bb6\u7814\u7a76\u4e8630\u79cd\u764c\u75c7\u7684\u8fd12\u4e07\u4e2a\u57fa\u56e0\uff0c\u63ea\u51fa\u4e86\u764c\u7ec6\u80de\u7684628\u4e2a\u201c\u547d\u95e8\u201d\u4e28\u79d1\u5b66\u5927\u53d1\u73b0"},"content":{"rendered":"
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\u8f6c\u81ea\u5947\u70b9\u7f51<\/p>\n


<\/p>\n

\u6628\u5929\uff0c\u82f1\u56fdWellcome Sanger Institute\u56e2\u961f\uff0c\u4ee5\u53ca\u7f8e\u56fdBroad Institute\u548cDana-Farber\u764c\u75c7\u7814\u7a76\u6240\u8054\u5408\u56e2\u961f\uff0c\u540c\u65f6\u5728\u9876\u7ea7\u671f\u520a\u300a\u81ea\u7136\u300b\u53d1\u8868\u91cd\u8981\u7814\u7a76\u6210\u679c\u3002<\/span><\/p>\n


<\/p>\n

\u764c\u75c7\u7684\u836f\u7269\u7814\u53d1\u548c\u6cbb\u7597\u53c8\u8fce\u6765\u91cd\u8981\u8fdb\u5c55\u3002<\/p>\n


<\/p>\n

\u7531Mathew J. Garnett\u548cKosuke Yusa\u9886\u8854\u7684Wellcome Sanger Institute\u56e2\u961f[1]\uff0c\u5229\u7528CRISPR-Cas9\u57fa\u56e0\u7f16\u8f91\u6280\u672f\uff0c\u6572\u6389\u4e86\u6a2a\u8de830\u4e2a\u764c\u79cd\u7684324\u79cd\u764c\u7ec6\u80de\u7cfb\u4e2d\u768418,009\u4e2a\u57fa\u56e0<\/strong>\u3002\u8fd9\u5de5\u4f5c\u91cf\u7b80\u76f4\u6ca1\u8c01\u4e86~<\/p>\n


<\/p>\n

\u8fd9\u4e5f\u662f\u79d1\u5b66\u5bb6\u9996\u6b21\u5b9e\u73b0\u4ece\u57fa\u56e0\u7ec4\u89c4\u6a21\u7684\u6c34\u5e73\u4e0a\uff0c\u4ee5\u6570\u636e\u9a71\u52a8\u7684\u65b9\u5f0f\uff0c\u5bfb\u627e\u6709\u6548\u7684\u6297\u764c\u9776\u70b9<\/strong>\u3002<\/p>\n


<\/p>\n

\"\u300a\u81ea\u7136\u300b\u53cc\u91cd\u78c5\uff1a\u730e\u6740\u764c\u7ec6\u80de\u57fa\u56e0\u540d\u5355\u53d1\u5e03\uff01\u79d1\u5b66\u5bb6\u7814\u7a76\u4e8630\u79cd\u764c\u75c7\u7684\u8fd12\u4e07\u4e2a\u57fa\u56e0\uff0c\u63ea\u51fa\u4e86\u764c\u7ec6\u80de\u7684628\u4e2a\u201c\u547d\u95e8\u201d\u4e28\u79d1\u5b66\u5927\u53d1\u73b0\"<\/p>\n

\u25b2 <\/strong><\/span><\/strong>Mathew J. Garnett\uff08\u5de6\uff09\u548cKosuke Yusa\uff08\u53f3\uff09\uff08\u6765\u6e90\uff1asanger.ac.uk\uff09<\/span><\/span><\/p>\n


<\/p>\n

\u91cd\u8981\u7684\u662f\uff0c\u4ed6\u4eec\u7684\u5de8\u5927\u5de5\u4f5c\u91cf\u8ba9\u764c\u7ec6\u80de\u5f7b\u5e95\u66b4\u9732\u4e86\u81ea\u5df1\u7684\u5f31\u70b9\uff0c\u6570\u5343\u4e2a\u764c\u7ec6\u80de\u751f\u957f\u4e0d\u53ef\u6216\u7f3a\u7684\u57fa\u56e0\u88ab\u53d1\u73b0\uff0c\u5176\u4e2d628\u4e2a\u57fa\u56e0<\/strong>\u662f\u975e\u5e38\u6709\u6f5c\u529b\u7684\u6297\u764c\u9776\u70b9<\/strong>\u3002\u4ed6\u4eec\u8fd8\u57fa\u4e8e\u81ea\u5df1\u5f00\u53d1\u7684\u8bc4\u4ef7\u4f53\u7cfb\uff0c\u7ed9\u8fd9628\u4e2a\u57fa\u56e0\u8bc4\u4e86\u4f18\u79c0\u7b49\u7ea7\uff0c\u8fd8\u4fe8\u7136\u4e00\u4e2a\u201c\u764c\u7ec6\u80de\u6b7b\u4ea1\u540d\u5355\u201d<\/strong>\u3002<\/p>\n


<\/p>\n

\u800c\u7531Adam J. Bass\u548cFrancisca Vazquez\u9886\u5bfc\u7684\u53e6\u4e00\u652f\u7814\u7a76\u56e2\u961f[2]\uff0c\u5219\u57fa\u4e8e\u4e24\u4e2a\u5927\u578b\u6570\u636e\u5e93\uff0c\u4e13\u95e8\u7ed9MSI\uff08\u5fae\u536b\u661f\u4e0d\u7a33\u5b9a\uff09\u627e\u201c\u5408\u6210\u81f4\u6b7b\u201d<\/strong><\/a>\u7684\u57fa\u56e0\u3002<\/p>\n


<\/p>\n

\u7ed3\u679c\u4e0eWRN\u57fa\u56e0\uff08\u7f16\u7801\u4e00\u79cdDNA\u87ba\u65cb\u9176\uff09\u4e0d\u671f\u800c\u9047\u3002\u800c\u4e14\u4ed6\u4eec\u8fd8\u5728\u5c0f\u9f20\u6a21\u578b\u4e2d\u8bc1\u5b9e\u4e86WRN\u548cMSI\u4e4b\u95f4\u7684\u5408\u6210\u81f4\u6b7b\u6297\u764c\u6548\u679c\u3002<\/strong>\u4e0eGarnett\u548cYusa\u56e2\u961f\u7684\u53d1\u73b0\u6697\u5408\u3002<\/strong><\/p>\n


<\/p>\n

\"\u300a\u81ea\u7136\u300b\u53cc\u91cd\u78c5\uff1a\u730e\u6740\u764c\u7ec6\u80de\u57fa\u56e0\u540d\u5355\u53d1\u5e03\uff01\u79d1\u5b66\u5bb6\u7814\u7a76\u4e8630\u79cd\u764c\u75c7\u7684\u8fd12\u4e07\u4e2a\u57fa\u56e0\uff0c\u63ea\u51fa\u4e86\u764c\u7ec6\u80de\u7684628\u4e2a\u201c\u547d\u95e8\u201d\u4e28\u79d1\u5b66\u5927\u53d1\u73b0\"<\/p>\n

\u25b2 <\/strong><\/span><\/strong>Adam J. Bass\uff08\u6765\u6e90\uff1adana-farber.org\uff09<\/span><\/span><\/p>\n


<\/p>\n

\u764c\u75c7\u662f\u5a01\u80c1\u4eba\u7c7b\u751f\u547d\u5065\u5eb7\u6570\u4e00\u6570\u4e8c\u7684\u6740\u624b\uff0c\u6bcf\u5e74\u5a01\u80c1\u5343\u4e07\u4eba\u7684\u751f\u547d\u5065\u5eb7\u3002<\/p>\n


<\/p>\n

\u867d\u7136\u4eba\u7c7b\u5df2\u7ecf\u4e0e\u764c\u75c7\u6597\u4e89\u4e86\u6570\u5343\u5e74\uff0c\u4f46\u6211\u4eec\u6cbb\u7597\u764c\u75c7\u7684\u65b9\u6cd5\u4f9d\u7136\u6709\u9650\u3002\u4f5c\u4e3a\u4e3b\u8981\u7684\u6cbb\u7597\u65b9\u6cd5\uff0c\u624b\u672f\u3001\u653e\u7597\u3001\u5316\u7597\u3001\u9776\u5411\u6cbb\u7597\u548c\u514d\u75ab\u6cbb\u7597\u7684\u6548\u679c\u4f9d\u7136\u6709\u9650\uff0c\u6709\u5927\u91cf\u7684\u60a3\u8005\u5bf9\u6cbb\u7597\u4e0d\u54cd\u5e94<\/strong>\u3002<\/p>\n


<\/p>\n

\u800c\u65b0\u836f\u7684\u7814\u53d1\u53c8\u56f0\u96be\u91cd\u91cd\u3002\u7531\u4e8e\u79d1\u5b66\u5bb6\u76ee\u524d\u5bf9\u764c\u75c7\u4e86\u89e3\u4ecd\u7136\u5341\u5206\u6709\u9650<\/strong>\uff0c\u8fd9\u4e5f\u5bfc\u81f4\u79d1\u5b66\u5bb6\u5f88\u96be\u627e\u5230\u6709\u6548\u7684\u6cbb\u7597\u9776\u70b9\u3002<\/p>\n


<\/p>\n

\u8fd9\u4e2a\u96be\u5ea6\u6709\u591a\u5927\uff0c\u6211\u4eec\u770b\u4e24\u4e2a\u6570\u636e\u5c31\u77e5\u9053\u4e86\u3002\u636e\u7edf\u8ba1\uff0c\u6bcf\u5f00\u53d1\u4e00\u4e2a\u6297\u764c\u65b0\u836f\u8017\u8d4410-20\u4ebf\u7f8e\u5143<\/strong>[3]\uff0c\u5373\u4fbf\u5982\u6b64\uff0c\u4ecd\u670990%\u4ee5\u4e0a<\/strong>\u7684\u5316\u5408\u7269\u5012\u5728\u4e34\u5e8a\u7814\u7a76\u9636\u6bb5[4]\u3002\u5728\u8bbe\u8ba1\u5408\u6210\u836f\u7269\u4e4b\u524d\uff0c\u627e\u5230\u4e00\u4e2a\u5408\u9002\u7684\u9776\u70b9\u663e\u5f97\u5c24\u4e3a\u91cd\u8981<\/strong>\u3002<\/p>\n


<\/p>\n

\u8fd9\u4e00\u70b9\uff0c\u6211\u4eec\u505a\u7684\u663e\u7136\u8fd8\u662f\u4e0d\u591f\u3002<\/p>\n


<\/p>\n

\"\u300a\u81ea\u7136\u300b\u53cc\u91cd\u78c5\uff1a\u730e\u6740\u764c\u7ec6\u80de\u57fa\u56e0\u540d\u5355\u53d1\u5e03\uff01\u79d1\u5b66\u5bb6\u7814\u7a76\u4e8630\u79cd\u764c\u75c7\u7684\u8fd12\u4e07\u4e2a\u57fa\u56e0\uff0c\u63ea\u51fa\u4e86\u764c\u7ec6\u80de\u7684628\u4e2a\u201c\u547d\u95e8\u201d\u4e28\u79d1\u5b66\u5927\u53d1\u73b0\"<\/p>\n

\u25b2 <\/strong><\/span><\/strong>Francisca Vazquez\uff08\u6765\u6e90\uff1abroadinstitute.org\uff09<\/span><\/span><\/p>\n


<\/p>\n

\u4e0d\u8fc7\u79d1\u6280\u7684\u53d1\u5c55\u7ed9\u6211\u4eec\u5e26\u6765\u4e86\u65b0\u7684\u673a\u9047\uff0c\u5c24\u5176\u662fCRISPR\u57fa\u56e0\u7f16\u8f91\u6280\u672f\u7684\u8bde\u751f\u3002\u8fd1\u5e74\u6765\uff0c\u5728\u5168\u4e16\u754c\u79d1\u5b66\u5bb6\u7684\u4e0d\u61c8\u52aa\u529b\u4e4b\u4e0b\uff0cCRISPR\u4e0d\u65ad\u88ab\u5347\u7ea7\u548c\u6539\u8fdb\u3002<\/p>\n


<\/p>\n

\u201cCRISPR\u662f\u4e00\u4e2a\u975e\u5e38\u5f3a\u5927\u7684\u5de5\u5177\uff0c5\u5e74\u4e4b\u524d\u65e0\u8bba\u5982\u4f55\u4e5f\u505a\u4e0d\u5230\u4eca\u5929\u8fd9\u4e2a\u89c4\u6a21\u548c\u7cbe\u5ea6<\/strong>\uff0c\u4eca\u5929\u7684CRISPR\u57fa\u56e0\u7f16\u8f91\u6280\u672f\u7ed9\u6211\u4eec\u4e00\u4e2a\u7edd\u4f73\u7684\u673a\u4f1a<\/strong>\uff0c\u53bb\u5f00\u53d1\u6297\u764c\u65b0\u836f\u3002\u201dKosuke Yusa\u8868\u793a[3]\u3002<\/p>\n


<\/p>\n

\u6b63\u662f\u7785\u51c6\u4e86\u8fd9\u4e2a\u673a\u4f1a\uff0cWellcome Sanger Institute\u624d\u8054\u5408GSK\uff0cEMBL-EBI\uff0cOpen Targets\u7b49\u7814\u7a76\u673a\u6784\u7684\u79d1\u5b66\u5bb6\uff0c\u8054\u5408\u5f00\u5c55\u4e86\u8fd9\u9879CRISPR\u7b5b\u9009\u6297\u764c\u9776\u70b9\u7684\u7814\u7a76\uff0c\u8fd9\u4e5f\u662f\u5168\u7403\u8303\u56f4\u5185\u89c4\u6a21\u6700\u5927\u7684\u51e0\u4e2a\u540c\u7c7b\u7814\u7a76\u4e4b\u4e00<\/strong>\u3002<\/p>\n


<\/p>\n

\"\u300a\u81ea\u7136\u300b\u53cc\u91cd\u78c5\uff1a\u730e\u6740\u764c\u7ec6\u80de\u57fa\u56e0\u540d\u5355\u53d1\u5e03\uff01\u79d1\u5b66\u5bb6\u7814\u7a76\u4e8630\u79cd\u764c\u75c7\u7684\u8fd12\u4e07\u4e2a\u57fa\u56e0\uff0c\u63ea\u51fa\u4e86\u764c\u7ec6\u80de\u7684628\u4e2a\u201c\u547d\u95e8\u201d\u4e28\u79d1\u5b66\u5927\u53d1\u73b0\"<\/p>\n

\u25b2 <\/strong><\/span><\/strong>CRISPR\u57fa\u56e0\u7f16\u8f91\u793a\u610f\u56fe\uff08\u6765\u6e90\uff1amichelsonmedical.org\uff09<\/span><\/p>\n


<\/p>\n

\u65e2\u7136\u8981\u5e72\uff0c\u90a3\u5c31\u5e72\u8106\u5e72\u7968\u5927\u7684\u3002<\/p>\n


<\/p>\n

\u4e3a\u4e86\u627e\u5230\u90a3\u4e9b\u764c\u7ec6\u80de\u751f\u957f\u5fc5\u9700\uff0c\u4e14\u4e0d\u5f71\u54cd\u6b63\u5e38\u7ec6\u80de\u7684\u5173\u952e\u57fa\u56e0\uff0c\u7814\u7a76\u56e2\u961f\u91c7\u53d6\u4e86\u5e7f\u6492\u7f51\u7684\u7b56\u7565\u3002<\/p>\n


<\/p>\n

\u4ed6\u4eec\u7d2f\u8ba1\u7528CRISPR-Cas9\u5e72\u6389\u4e8618009\u4e2a\u57fa\u56e0\uff0c\u8fd9\u4e9b\u57fa\u56e0\u5206\u5e03\u572819\u4e2a\u7ec4\u7ec7\u768430\u4e2a\u764c\u75c7\u7c7b\u578b\u7684324\u4e2a\u764c\u7ec6\u80de\u7cfb\u4e2d<\/strong>\u3002\u8fd9\u4e9b\u764c\u7ec6\u80de\u7cfb\u6709\u4e2a\u7279\u70b9\uff0c\u57fa\u56e0\u7ec4\u90fd\u88ab\u9ad8\u5ea6\u6ce8\u91ca[5]\uff0c\u57fa\u672c\u56ca\u62ec\u4e86\u764c\u7ec6\u80de\u7684\u5206\u5b50\u7279\u5f81[6]\u3002<\/p>\n


<\/p>\n

\"\u300a\u81ea\u7136\u300b\u53cc\u91cd\u78c5\uff1a\u730e\u6740\u764c\u7ec6\u80de\u57fa\u56e0\u540d\u5355\u53d1\u5e03\uff01\u79d1\u5b66\u5bb6\u7814\u7a76\u4e8630\u79cd\u764c\u75c7\u7684\u8fd12\u4e07\u4e2a\u57fa\u56e0\uff0c\u63ea\u51fa\u4e86\u764c\u7ec6\u80de\u7684628\u4e2a\u201c\u547d\u95e8\u201d\u4e28\u79d1\u5b66\u5927\u53d1\u73b0\"<\/p>\n

\u25b2 <\/strong><\/span><\/strong>\u770b\u4e0a\u53bb\u5f88\u590d\u6742\u7684\u5b9e\u9a8c\u8fc7<\/span>\u7a0b[1]<\/span><\/span><\/p>\n


<\/p>\n

\u7ecf\u8fc7\u521d\u6b65\u7684\u7b5b\u67e5\uff0c\u4ed6\u4eec\u786e\u5b9e\u5f97\u5230\u4e86\u4e0d\u5c11\u76ee\u6807\u57fa\u56e0\uff0c\u4e0d\u8fc7\u521d\u6b65\u7684\u7ed3\u679c\u5e76\u4e0d\u80fd\u544a\u8bc9\u79d1\u5b66\u5bb6\u54ea\u4e9b\u57fa\u56e0\u66f4\u9002\u5408\u4f5c\u4e3a\u6297\u764c\u9776\u70b9\u3002<\/p>\n


<\/p>\n

\u56e0\u6b64\uff0c\u4ed6\u4eec\u53c8\u5f00\u53d1\u4e86\u4e00\u4e2a\u8ba1\u7b97\u6846\u67b6\uff0c\u8fd9\u4e2a\u6846\u67b6\u6574\u5408\u4e86\u591a\u4e2a\u8bc1\u636e\u7ebf\uff0c\u4e3a\u6bcf\u4e2a\u57fa\u56e0\u5206\u914d\u4e86\u4e00\u4e2a\u8303\u56f4\u4ece0\u5230100\u7684<\/strong>\u4f18\u5148\u7ea7\u5206\u6570\u3002\u7ecf\u8fc7\u8fdb\u4e00\u6b65\u7684\u5206\u6790\uff0c\u6392\u9664\u90a3\u4e9b\u6709\u6f5c\u5728\u6bd2\u6027\u7684\u9776\u70b9\uff0c<\/strong>\u79d1\u5b66\u5bb6\u7ec8\u4e8e\u751f\u6210\u4e86\u4e00\u4e2a\u5305\u542b628\u4e2a\u57fa\u56e0\u7684\u201c\u730e\u6740\u764c\u7ec6\u80de\u57fa\u56e0\u540d\u5355\u201d<\/strong>\u3002<\/p>\n


<\/p>\n

\"\u300a\u81ea\u7136\u300b\u53cc\u91cd\u78c5\uff1a\u730e\u6740\u764c\u7ec6\u80de\u57fa\u56e0\u540d\u5355\u53d1\u5e03\uff01\u79d1\u5b66\u5bb6\u7814\u7a76\u4e8630\u79cd\u764c\u75c7\u7684\u8fd12\u4e07\u4e2a\u57fa\u56e0\uff0c\u63ea\u51fa\u4e86\u764c\u7ec6\u80de\u7684628\u4e2a\u201c\u547d\u95e8\u201d\u4e28\u79d1\u5b66\u5927\u53d1\u73b0\"<\/p>\n

\u25b2<\/strong><\/span><\/strong> <\/strong><\/span><\/strong>\u201d\u6b7b\u4ea1\u540d\u5355\u201c[1]<\/span><\/span>\uff08\u770b\u770b\u6709\u591a\u5c11\u8001\u670b\u53cb\uff09<\/span><\/span><\/p>\n


<\/p>\n

\u5176\u4e2d\u6709457\uff0874%\uff09\u4e2a\u53ea\u51fa\u73b0\u5728\u4e00\u79cd\uff0856%\uff09\u6216\u4e24\u79cd\uff0818%\uff09\u764c\u75c7\u7c7b\u578b\u4e2d<\/strong>\u3002\u800c\u4e14\uff0c\u5728\u8fd9\u4e9b\u57fa\u56e0\u91cc\u9762\uff0c\u6709120\u4e2a\uff0819%\uff09\u81f3\u5c11\u6709\u4e00\u4e2a\u76f8\u5173\u8054\u7684\u751f\u7269\u6807\u5fd7\u7269<\/strong>\uff0c\u56e0\u6b64\u5b83\u4eec\u6210\u4e3a\u836f\u7269\u9776\u70b9\u7684\u53ef\u80fd\u6027\u8981\u66f4\u5927\u4e00\u4e9b\u3002<\/p>\n


<\/p>\n

\"\u300a\u81ea\u7136\u300b\u53cc\u91cd\u78c5\uff1a\u730e\u6740\u764c\u7ec6\u80de\u57fa\u56e0\u540d\u5355\u53d1\u5e03\uff01\u79d1\u5b66\u5bb6\u7814\u7a76\u4e8630\u79cd\u764c\u75c7\u7684\u8fd12\u4e07\u4e2a\u57fa\u56e0\uff0c\u63ea\u51fa\u4e86\u764c\u7ec6\u80de\u7684628\u4e2a\u201c\u547d\u95e8\u201d\u4e28\u79d1\u5b66\u5927\u53d1\u73b0\"<\/p>\n

\u25b2 <\/strong><\/span><\/strong>\u9776\u70b9\uff08\u4e0a\u9762\u4e00\u884c\uff09\u548c\u5bf9\u5e94\u7684\u751f\u7269\u6807\u5fd7\u7269\uff08\u4e0b\u9762\u4e00\u884c\uff09[1]<\/span><\/p>\n

\uff08WRN\u548cMSI\u8fd9\u5bf9\u642d\u6863\u89e6\u9876\u4e86~\uff09<\/span><\/span><\/p>\n


<\/p>\n

\u968f\u540e\uff0c\u7814\u7a76\u4eba\u5458\u53c8\u5c06\u8fd9628\u4e2a\u9776\u70b9\u5206\u6210\u4e861\u30012\u30013\u4e09\u4e2a\u7ec4\u3002\u5176\u4e2d\u7b2c1\u7ec4\u670940\u4e2a\u57fa\u56e0<\/strong>\uff0c\u5b83\u4eec\u8981\u4e48\u662f\u5df2\u7ecf\u6709\u83b7\u6279\u836f\u7269\u4e86\uff0c\u8981\u4e48\u662f\u6709\u836f\u7269\u6b63\u5728\u5f00\u5c55\u4e34\u5e8a\u7814\u7a76\uff1b\u7b2c2\u7ec4\u6709277\u4e2a\u57fa\u56e0<\/strong>\uff0c\u8fd9\u4e9b\u76ee\u6807\u9776\u70b9\u76ee\u524d\u6ca1\u6709\u836f\u7269\uff0c\u4f46\u6709\u57fa\u7840\u7814\u7a76\u8bc1\u660e\uff0c\u5b83\u4eec\u786e\u5b9e\u6709\u6f5c\u529b\uff1b\u7b2c3\u7ec4\u5305\u542b311\u4e2a\u9776\u70b9<\/strong>\uff0c\u8fd9\u4e9b\u9776\u70b9\u4e0d\u4ec5\u76ee\u524d\u6ca1\u6709\u5728\u7814\u836f\u7269\uff0c\u751a\u81f3\u8fde\u652f\u6491\u7684\u8bc1\u636e\u90fd\u5c11\u6709\uff0c\u4e5f\u5c31\u662f\u5168\u65b0\u7684\u53d1\u73b0<\/strong>\u3002<\/p>\n


<\/p>\n

\"\u300a\u81ea\u7136\u300b\u53cc\u91cd\u78c5\uff1a\u730e\u6740\u764c\u7ec6\u80de\u57fa\u56e0\u540d\u5355\u53d1\u5e03\uff01\u79d1\u5b66\u5bb6\u7814\u7a76\u4e8630\u79cd\u764c\u75c7\u7684\u8fd12\u4e07\u4e2a\u57fa\u56e0\uff0c\u63ea\u51fa\u4e86\u764c\u7ec6\u80de\u7684628\u4e2a\u201c\u547d\u95e8\u201d\u4e28\u79d1\u5b66\u5927\u53d1\u73b0\"<\/p>\n

\u25b2 <\/strong><\/span><\/strong>\u62ff4\u4e2a\u764c\u79cd\u6765\u4e3e\u4e2a\u4f8b\u5b50[1]<\/span><\/span><\/span><\/p>\n


<\/p>\n

\u7814\u7a76\u4eba\u5458\u4e3a\u4e86\u68c0\u9a8c\u7814\u7a76\u6210\u679c\u7684\u9760\u8c31\u7a0b\u5ea6\uff0c\u4ece\u7b2c2\u7ec4\u4e2d\u62ce\u51fa\u4e00\u4e2a\u540d\u4e3aWRN\u9776\u70b9\uff0c\u548c\u5bf9\u5e94\u7684\u6807\u5fd7\u7269MSI\u505a\u4e86\u4e2a\u5c0f\u9a8c\u8bc1\u3002\u7ed3\u679c\u5728\u7ec6\u80de\u6c34\u5e73\uff0c\u4ee5\u53ca\u6a21\u5f0f\u5c0f\u9f20\u8eab\u4e0a\u8bc1\u5b9e\uff0cWRN\u548cMSI\u662f\u4e00\u5bf9\u201c\u5408\u6210\u81f4\u6b7b\u201d\u7684\u597d\u642d\u6863<\/strong>\u3002<\/p>\n


<\/p>\n

\u201c\u6211\u4eec\u8fd9\u4e2a\u7814\u7a76\u662f\u60f3\u627e\u5230\u764c\u7ec6\u80de\u7684\u6240\u6709\u5f31\u70b9\uff0c\u5e2e\u52a9\u5927\u5bb6\u8ba4\u6e05\u764c\u75c7\uff0c\u5bfb\u627e\u66f4\u6709\u6548\u7684\u6297\u764c\u9776\u70b9\u3002\u201dMathew J. Garnett\u8868\u793a[3]\uff0c\u201c\u4e0e\u6b64\u540c\u65f6\uff0c\u6211\u4eec\u7684\u8fd9\u4e9b\u5de5\u5177\u5c06\u4f1a\u514d\u8d39\u63d0\u4f9b\u7ed9\u5168\u4e16\u754c\u7684\u80bf\u7624\u5b66\u5bb6\uff0c\u5e2e\u52a9\u4ed6\u4eec\u7814\u7a76\u66f4\u591a\u7684\u80bf\u7624\u7c7b\u578b<\/strong>\u3002\u201d<\/span><\/p>\n


<\/p>\n

\"\u300a\u81ea\u7136\u300b\u53cc\u91cd\u78c5\uff1a\u730e\u6740\u764c\u7ec6\u80de\u57fa\u56e0\u540d\u5355\u53d1\u5e03\uff01\u79d1\u5b66\u5bb6\u7814\u7a76\u4e8630\u79cd\u764c\u75c7\u7684\u8fd12\u4e07\u4e2a\u57fa\u56e0\uff0c\u63ea\u51fa\u4e86\u764c\u7ec6\u80de\u7684628\u4e2a\u201c\u547d\u95e8\u201d\u4e28\u79d1\u5b66\u5927\u53d1\u73b0\"<\/p>\n

\u25b2 <\/strong><\/span><\/strong>\u8fd9\u5f20\u56fe\u6697\u85cfWRN\u548cMSI\u4e4b\u95f4\u7684\u5173\u7cfb[1]<\/span><\/span><\/span><\/p>\n


<\/p>\n

\u4e0eGarnett\u548cYusa\u56e2\u961f\u7684\u51fa\u53d1\u70b9\u4e0d\u540c\uff0cBroad Institute\u7684\u79d1\u5b66\u5bb6\u4eec\u53d7\u5230PARP\u6291\u5236\u5242\u5408\u6210\u81f4\u6b7b\u6297\u764c\u7684\u542f\u53d1\uff0c\u4ece\u4e00\u5f00\u59cb\u5c31\u8ba4\u5b9a\u4e86MSI\u662f\u4e2a\u597d\u6807\u5fd7\u7269<\/strong>\uff0c\u5e0c\u671b\u80fd\u4ece\u764c\u7ec6\u80de\u7684\u57fa\u56e0\u7ec4\u4e2d\u627e\u5230\u4e0eMSI\u6709\u5408\u6210\u81f4\u6b7b\u6548\u679c\u7684\u65b0\u9776\u70b9\u3002<\/p>\n


<\/p>\n

\u4ed6\u4eec\u628a\u76ee\u5149\u76ef\u5728\u4e24\u4e2a\u73b0\u6210\u7684\u764c\u75c7\u57fa\u56e0\u7ec4\u7814\u7a76\u6570\u636e\u5e93\u4e0a\u3002\u4e00\u4e2a\u53ebDepMap<\/strong>\uff0c\u662f\u4e2aCRISPR-Cas9\u57fa\u56e0\u6572\u9664\u6570\u636e\u5e93\uff1b\u53e6\u4e00\u4e2a\u53ebProject DRIVE<\/strong>\uff0c\u662f\u4e2aRNA\u6c89\u9ed8\u6570\u636e\u5e93\u3002\u6570\u636e\u90fd\u662f\u73b0\u6210\u7684\uff0c\u653e\u624b\u5206\u6790\u5373\u53ef\u3002<\/p>\n


<\/p>\n

\"\u300a\u81ea\u7136\u300b\u53cc\u91cd\u78c5\uff1a\u730e\u6740\u764c\u7ec6\u80de\u57fa\u56e0\u540d\u5355\u53d1\u5e03\uff01\u79d1\u5b66\u5bb6\u7814\u7a76\u4e8630\u79cd\u764c\u75c7\u7684\u8fd12\u4e07\u4e2a\u57fa\u56e0\uff0c\u63ea\u51fa\u4e86\u764c\u7ec6\u80de\u7684628\u4e2a\u201c\u547d\u95e8\u201d\u4e28\u79d1\u5b66\u5927\u53d1\u73b0\"<\/p>\n

\u25b2 <\/strong><\/span><\/strong>DepMap\u662f\u4e00\u4e2a\u5f88\u91cd\u8981\u7684\u6570\u636e\u5e93\uff0c\u5927\u5bb6\u6709\u5fc5\u8981\u8ba4\u8bc6\u4e00\u4e0b\uff08depmap.org\uff09<\/span><\/span><\/span><\/p>\n


<\/p>\n

\u5f88\u5feb\u4ed6\u4eec\u5c31\u53d1\u73b0\uff0c73%\u5b58\u5728MSI\u7684\u764c\u7ec6\u80de\u682a\u7cfb\u7684\u751f\u5b58\u79bb\u4e0d\u5f00WRN<\/strong>\uff0c\u76f8\u53cd\uff0c\u5728\u6ca1\u6709MSI\u7684\u764c\u7ec6\u80de\u7cfb\u4e2d\uff0cWRN\u88ab\u6572\u9664\u6216\u6c89\u9ed8\u4e0d\u5f71\u54cd\u764c\u7ec6\u80de\u7684\u751f\u957f<\/strong>\u3002<\/p>\n


<\/p>\n

\u5178\u578b\u7684\u6297\u764c\u597d\u9776\u70b9<\/strong>~<\/p>\n


<\/p>\n

\u4e3a\u4e86\u8fdb\u4e00\u6b65\u8bc1\u5b9eWRN\u4e0eMSI\u4e4b\u95f4\u7684\u5408\u6210\u81f4\u6b7b\u5173\u7cfb\uff0c\u7814\u7a76\u4eba\u5458\u9996\u5148\u5728\u764c\u7ec6\u80de\u7cfb\u4e2d\u6c89\u9ed8WRN\u7684\u8868\u8fbe\uff0c\u786e\u8ba4\u4e86WRN\u5bf9\u5b58\u5728MSI\u764c\u7ec6\u80de\u7684\u91cd\u8981\u6027\uff1b\u968f\u540e\u4ed6\u4eec\u5728\u5c0f\u9f20\u6a21\u578b\u4e0a\u8bc1\u5b9e\uff0c\u6291\u5236WRN\u53ef\u4ee5\u663e\u8457\u51cf\u7f13\u5c0f\u9f20MSI\u764c\u75c7\u7684\u751f\u957f\u3002<\/strong>\u4ed6\u4eec\u8fd8\u5728\u4eba\u4f53\u7ed3\u80a0\u764c\u884d\u751f\u80bf\u7624\u6a21\u578b\u4e2d\u8bc1\u5b9e\uff0c\u643a\u5e26MSI\u7684\u7ed3\u80a0\u764c\u5bf9WRN\u6709\u4e25\u91cd\u7684\u4f9d\u8d56\u6027<\/strong>\u3002<\/p>\n


<\/p>\n

WRN\u662f\u4e2a\u597d\u9776\u70b9\u3002<\/p>\n


<\/p>\n

\"\u300a\u81ea\u7136\u300b\u53cc\u91cd\u78c5\uff1a\u730e\u6740\u764c\u7ec6\u80de\u57fa\u56e0\u540d\u5355\u53d1\u5e03\uff01\u79d1\u5b66\u5bb6\u7814\u7a76\u4e8630\u79cd\u764c\u75c7\u7684\u8fd12\u4e07\u4e2a\u57fa\u56e0\uff0c\u63ea\u51fa\u4e86\u764c\u7ec6\u80de\u7684628\u4e2a\u201c\u547d\u95e8\u201d\u4e28\u79d1\u5b66\u5927\u53d1\u73b0\"<\/p>\n

\u25b2 <\/strong><\/span><\/strong>WRN\u5f3a\u52bf\u9886\u8dd1\u4e0eMSI\u7684\u5173\u7cfb[2]<\/span><\/span><\/p>\n


<\/p>\n

\u9519\u914d\u4fee\u590d\u662f\u7ef4\u6301\u7ec6\u80de\u57fa\u56e0\u7ec4\u7a33\u5b9a\u7684\u91cd\u8981\u673a\u5236\uff0c\u5982\u679c\u9519\u914d\u4fee\u590d\u76f8\u5173\u57fa\u56e0\u53d1\u751f\u7a81\u53d8\uff0cDNA\u5728\u590d\u5236\u8fc7\u7a0b\u4e2d\u53d1\u751f\u7684\u9519\u8bef\u5c31\u6ca1\u6709\u529e\u6cd5\u53ca\u65f6\u4fee\u590d\uff0cMSI\u5c31\u51fa\u73b0\u4e86\uff0c\u8fd9\u4e5f\u662f\u764c\u75c7\u53d1\u751f\u7684\u539f\u56e0\u4e4b\u4e00\u3002<\/p>\n


<\/p>\n

\u5176\u5b9e\uff0c\u643a\u5e26MSI\u7684\u764c\u75c7\u60a3\u8005\u662f\u6709\u836f\u53ef\u7528\u7684\uff0c\u6bd5\u7adfFDA\u5df2\u7ecf\u6279\u51c6PD-1\u6297\u4f53\u7528\u4e8eMSI\u80bf\u7624\u7684\u6cbb\u7597\u3002\u4e0d\u8fc7\u5462\uff0c\u4ecd\u7136\u53ea\u6709\u4e00\u5c0f\u90e8\u5206\u60a3\u8005\u80fd\u4ece\u4e2d\u83b7\u76ca\uff0c\u5927\u90e8\u5206\u6709MSI\u7684\u60a3\u8005\u5bf9PD-1\u6297\u4f53\u662f\u4e0d\u54cd\u5e94\u7684<\/strong>\u3002<\/p>\n


<\/p>\n

\u800cMSI\u5728\u6d88\u5316\u7cfb\u7edf\u80bf\u7624\uff0c\u5c24\u5176\u662f\u809d\u764c\u3001\u80c3\u764c\u548c\u80a0\u764c\uff0c\u4ee5\u53ca\u5b50\u5bab\u5185\u819c\u764c<\/strong>\u4e2d\u5360\u6bd4\u662f\u6bd4\u8f83\u9ad8\u7684[7]\u3002\u56e0\u6b64\uff0c\u8fd8\u6709\u5f88\u5927\u4e00\u90e8\u5206\u60a3\u8005\u7684\u9700\u6c42\u6ca1\u6709\u5f97\u5230\u6ee1\u8db3\u3002<\/p>\n


<\/p>\n

\n

\u25b2 <\/strong><\/span><\/strong>MSI\u7684\u5206\u5e03[7]<\/span><\/span><\/p>\n


<\/p>\n

\u8fd9\u6b21\uff0cWRN\u7684\u51fa\u73b0\uff0c\u8ba9\u8fd9\u90e8\u5206\u60a3\u8005\u6709\u4e86\u65b0\u7684\u5e0c\u671b\uff0c\u800c\u4e14\u4e00\u65e6\u6210\u836f\uff0c\u4f7f\u7528\u7684\u4f34\u968f\u8bca\u65ad\u4e5f\u4f1a\u975e\u5e38\u7b80\u5355\uff0c\u666e\u901aPCR\u7684\u65b9\u6cd5\u5373\u53ef\u5b8c\u6210\u68c0\u6d4b\u3002<\/p>\n


<\/p>\n

\u5b9e\u9645\u4e0a\uff0c\u51e0\u4e4e\u5728\u540c\u4e00\u65f6\u95f4\uff0c\u6211\u4eec\u4e4b\u524d\u4ecb\u7ecd\u8fc7\u7684\u836f\u7269\u7814\u53d1\u516c\u53f8IDEAYA Biosciences<\/strong><\/a>\u4e5f\u4eceDepMap\u6570\u636e\u5e93\u4e2d\u53d1\u73b0\u4e86WRN\u4e0eMSI\u4e4b\u95f4\u7684\u5408\u6210\u81f4\u6b7b\u5173\u7cfb\u3002<\/p>\n


<\/p>\n

\u5982\u6b64\u770b\u6765\uff0c\u9776\u5411WRN\u7684\u5408\u6210\u81f4\u6b7b\u6297\u764c\u836f\u7269\u7684\u51fa\u73b0\uff0c\u53ea\u662f\u65f6\u95f4\u7684\u95ee\u9898\u3002<\/p>\n


<\/p>\n

\u53c2\u8003\u8d44\u6599\uff1a<\/span><\/p>\n

[1].Fiona M. Behan, Francesco Iorio, et al. Prioritization of cancer therapeutic targets using CRISPR\u2013Cas9 screens[J]. Nature, 2019.  DOI\uff1a<\/strong><\/span>10.1038\/s41586-019-1103-9.<\/span><\/strong><\/p>\n

[2].Edmond M. Chan, Tsukasa Shibue, James M. McFarland, et al. WRN helicase is a synthetic lethal target in microsatellite unstable cancers[J]. Nature, 2019.  DOI\uff1a<\/strong><\/span>10.1038\/s41586-019-1102-x.<\/span><\/strong><\/p>\n

[3].https:\/\/www.sanger.ac.uk\/news\/view\/new-cancer-drug-targets-accelerate-path-precision-medicine<\/span><\/p>\n

[4].Hay M, Thomas D W, Craighead J L, et al. Clinical development success rates for investigational drugs[J]. Nature Biotechnology, 2014, 32(1): 40-51.  DOI\uff1a<\/strong><\/span>10.1038\/nbt.2786.<\/span><\/strong><\/p>\n

[5].Der Meer D V, Barthorpe S, Yang W, et al.  Model Passports\u2014a hub for clinical, genetic and functional datasets of preclinical cancer models[J]. Nucleic Acids Research, 2019.  DOI\uff1a<\/strong><\/span>10.1093\/nar\/gky872.<\/span><\/strong><\/p>\n

[6].Iorio F, Knijnenburg T, Vis D J, et al. A Landscape of Pharmacogenomic Interactions in Cancer[J]. , 2016, 166(3): 740-754.  DOI\uff1a<\/strong><\/span>10.1016\/j.cell.2016.06.017.<\/span><\/strong><\/p>\n

[7].Dudley J C, Lin M, Le D T, et al. Microsatellite Instability as a Biomarker for PD-1 Blockade[J]. Clinical Cancer Research, 2016, 22(4): 813-820.  DOI\uff1a<\/strong><\/span>10.1158\/1078-0432.CCR-15-1678.<\/span><\/strong><\/p>\n

[8].Kategaya L, Perumal S K, Hager J H, et al. Werner Syndrome Helicase Is Required for the Survival of Cancer s with Microsatellite Instability[J]. iScience, 2019.  DOI\uff1a<\/strong><\/span>10.1016\/j.isci.2019.02.006.<\/span><\/strong><\/span><\/p>\n<\/section>\n<\/section>\n<\/section>\n<\/section><\/div>\n","protected":false},"excerpt":{"rendered":"

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