{"id":81567,"date":"2022-10-15T16:11:00","date_gmt":"2022-10-15T09:11:00","guid":{"rendered":"https:\/\/www.xinwengao.com\/cn\/pr\/2022101516110081567"},"modified":"2022-10-15T22:11:47","modified_gmt":"2022-10-15T14:11:47","slug":"%e5%86%8d%e8%8e%b7%e9%87%8d%e8%a6%81%e6%88%90%e6%9e%9c%ef%bc%9a%e9%82%a6%e8%80%80%e7%94%9f%e7%89%a9nature-chemical-biology%e5%8f%91%e6%96%87%ef%bc%8c%e5%bc%80%e5%8f%91%e7%b2%be%e5%87%86%e5%ae%89","status":"publish","type":"post","link":"https:\/\/www.xinwengao.com\/cn\/pr\/2022101516110081567","title":{"rendered":"\u518d\u83b7\u91cd\u8981\u6210\u679c\uff1a\u90a6\u8000\u751f\u7269Nature Chemical Biology\u53d1\u6587\uff0c\u5f00\u53d1\u7cbe\u51c6\u5b89\u5168\u7684\u65b0\u578b\u817a\u560c\u5464\u78b1\u57fa\u7f16\u8f91\u5668 — "ABE9""},"content":{"rendered":"

\u4e0a\u6d77<\/span>2022\u5e7410\u670815\u65e5<\/span> \/\u7f8e\u901a\u793e\/ — \u78b1\u57fa\u7f16\u8f91\u6280\u672f\u6700\u65e9\u7531\u54c8\u4f5b\u5927\u5b66David R. Liu\u56e2\u961f\u5f00\u53d1\uff0c\u4e3b\u8981\u5206\u4e3a\u4e24\u7c7b\uff1a\u80de\u5627\u5576\u78b1\u57fa\u7f16\u8f91\u5668(CBE)\u4e0e\u817a\u560c\u5464\u78b1\u57fa\u7f16\u8f91\u5668(ABE)\uff0c\u5206\u522b\u7531\u80de\u5627\u5576\u8131\u6c28\u9176\u6216\u6539\u9020\u7684\u817a\u560c\u5464\u8131\u6c28\u9176\u4e0eCas9\u9176\u6d3b\u7a81\u53d8\u578b\u86cb\u767d\uff08nickase Cas9\uff09\u878d\u5408\u800c\u6765\u3002\u76ee\u524d\uff0cCBE\u4e0eABE\u867d\u5df2\u5728\u591a\u4e2a\u7269\u79cd\u4e2d\u5f97\u5230\u5e7f\u6cdb\u5e94\u7528\u3002\u7136\u800c\u901a\u8fc7\u4e0d\u5c11\u5b9e\u9a8c\u7814\u7a76\u8868\u660e\u5b83\u4eec\u4ecd\u5b58\u5728\u4e25\u91cd\u7684\u968f\u673a\u8131\u9776\u73b0\u8c61\uff0c\u672a\u5f97\u5230\u5b8c\u5168\u89e3\u51b3\u3002<\/p>\n

2022\u5e7410\u670814\u65e5\uff0c\u805a\u7126\u4e8e\u57fa\u56e0\u548c\u7ec6\u80de\u6cbb\u7597\u7684\u4e0a\u6d77\u90a6\u8000\u751f\u7269\u79d1\u6280\u6709\u9650\u516c\u53f8<\/b>\uff08\u4ee5\u4e0b\u7b80\u79f0"\u90a6\u8000\u751f\u7269"\uff09\u5ba3\u5e03\uff0c\u4e0e\u534e\u4e1c\u5e08\u8303\u5927\u5b66\u674e\u5927\u529b\u6559\u6388\u53ca\u5218\u660e\u8000\u6559\u6388\u56e2\u961f\u5408\u4f5c\u5f00\u53d1\u5e76\u547d\u540d\u4e86\u4e00\u79cd\u7cbe\u51c6\u4e14\u5b89\u5168\u7684\u65b0\u578b\u817a\u560c\u5464\u78b1\u57fa\u7f16\u8f91\u5668 — "<\/b>ABE9<\/b>"\uff0c\u80fd\u591f\u6709\u6548\u89e3\u51b3ABE<\/b>\u4e34\u5e8a\u5e94\u7528\u5b58\u5728\u7684\u5404\u7c7b\u8131\u9776\u9690\u60a3\u548c\u5b89\u5168\u6027\u95ee\u9898\uff0c<\/b>\u7406\u8bba\u4e0a\u5c06\u4e3a\u8fd150%<\/b>\u9057\u4f20\u81f4\u75c5\u6027<\/b>SNVs<\/b>\u7684\u7ea0\u6b63\u63d0\u4f9b\u4e86\u65b0\u7684\u7cbe\u51c6\u9776\u5411\u5de5\u5177\u3002<\/b>\u8be5\u9879\u7814\u7a76\u6210\u679c\u4e8e10\u670813\u65e5\u6b63\u5f0f\u5728\u56fd\u9645\u5b66\u672f\u671f\u520aNature Chemical Biology<\/i><\/b>\u4e0a\u53d1\u8868\u3002\u53ef\u4ee5\u8bf4\uff0c\u8fd9\u4e00\u53d1\u73b0\u5bf9\u63d0\u5347<\/b>ABE<\/b>\u5de5\u5177\u7684\u5b89\u5168\u6027\uff0c\u62d3\u5bbd\u5176\u9002\u7528\u8303\u56f4\uff0c\u63a8\u52a8\u5176\u5728\u57fa\u56e0\u6cbb\u7597\u4e2d\u7684\u5e94\u7528\u53ca\u540e\u7eed\u7684\u4e34\u5e8a\u8f6c\u5316\u5747\u5177\u6709\u91cd\u8981\u610f\u4e49\u3002<\/b><\/p>\n

\n

\"Nature<\/a>
Nature Chemical Biology\u53d1\u6587<\/span><\/p>\n<\/p><\/div>\n

\u8bba\u6587\u94fe\u63a5\uff1ahttps:\/\/www.nature.com\/articles\/s41589-022-01163-8<\/a><\/u><\/p>\n

\u503c\u5f97\u4e00\u63d0\u7684\u662f\uff0cABE9<\/b>\u4f5c\u4e3a\u65b0\u4e00\u4ee3\u6700\u5177\u6709\u4e34\u5e8a\u9002\u7528\u6027\u7684\u4ea7\u54c1\uff0c\u5df2\u63d0\u524d\u5b8c\u6210\u6838\u5fc3\u4e13\u5229\u7533\u8bf7\uff0c\u672a\u6765\u4e13\u5229\u5e03\u5c40\u5c06\u8986\u76d6\u5168\u7403\u4e3b\u6d41\u5e02\u573a\u3002<\/b>\u76ee\u524d\uff0c\u90a6\u8000\u751f\u7269\u5728ABE\u6280\u672f\u9886\u57df\u62e5\u6709\u6301\u7eed\u800c\u6df1\u539a\u7684\u4e13\u5229\u5e03\u5c40\u79ef\u7d2f\uff0c\u5728\u5168\u7403\u8303\u56f4\u5185\u5df2\u83b7\u5f97\u6388\u6743\u7684\u78b1\u57fa\u7f16\u8f91\u5668\u4e13\u5229\u8fbe\u591a\u4e2a\u540c\u65cf\u3002<\/p>\n

\u65b0\u578b\u817a\u560c\u5464\u78b1\u57fa\u7f16\u8f91\u5668"ABE9<\/b>"\uff1a\u7cbe\u51c6\u4e14\u5b89\u5168\uff0c\u4e34\u5e8a\u5e94\u7528\u6f5c\u529b\u5de8\u5927<\/b><\/p>\n

DNA\u78b1\u57fa\u7f16\u8f91\u5668\u7531\u4e8e\u53ef\u4ee5\u5728\u4e0d\u4ea7\u751fDNA\u53cc\u94fe\u65ad\u88c2(DSB)\u3001\u4e0d\u9700\u8981\u4f9b\u4f53DNA\u6a21\u677f\u7684\u60c5\u51b5\u4e0b\u9ad8\u6548\u5730\u50ac\u5316\u78b1\u57fa\u8f6c\u6362\uff0c\u5728\u79cd\u8d28\u6539\u826f\u548c\u57fa\u56e0\u6cbb\u7597\u4e2d\u88ab\u5bc4\u4e88\u539a\u671b\u3002\u7136\u800c\u7531David R. Liu\u56e2\u961f\u5f00\u53d1\u7684\u521d\u4ee3ABE7.10\u7684\u7f16\u8f91\u6548\u7387\u5bf9\u4e8e\u5f88\u591a\u9776\u70b9\u800c\u8a00\u5374\u4e0d\u5c3d\u5982\u4eba\u610f\uff0c\u867d\u7136David Liu\u7b49\u8bfe\u9898\u7ec4\u901a\u8fc7\u5206\u5b50\u8fdb\u5316\u83b7\u5f97\u4e86\u66f4\u9ad8\u6d3b\u6027\u7684ABE8\uff08ABE8e \u548cABE8s\uff09\uff0c\u4f46\u662fABE\u4e00\u4e9b\u56fa\u6709\u7684\u7f3a\u9677\u5374\u5e76\u6ca1\u6709\u89e3\u51b3\u3002\u4f8b\u5982\uff0cABE\u5f15\u8d77\u7684\u5927\u91cf\u968f\u673a\u7684RNA\u8131\u9776\u7f16\u8f91\uff0c\u7531\u4e8e\u7f16\u8f91\u7a97\u53e3\u8f83\u5bbd\u5f15\u8d77\u975e\u76ee\u6807\u78b1\u57fa\u6539\u53d8\u800c\u4ea7\u751f\u65c1\u89c2\u8005\u6548\u5e94\u4ee5\u53caABE\u4f1a\u5728\u7279\u5b9a\u7684TCN motif\u7684\u78b1\u57fa\u5e8f\u5217\u4e2d\u8bf1\u53d1\u80de\u5627\u5576\u78b1\u57fa\u8f6c\u6362\u3002<\/p>\n

\u8be5\u7814\u7a76\u9996\u5148\u8bc1\u660e\u4e86\u9ad8\u6d3b\u6027\u7684ABE8e\u5f15\u53d1\u4e86\u66f4\u4e25\u91cd\u7684\u65c1\u89c2\u8005\u6548\u5e94\u4ee5\u53caCas9\u975e\u4f9d\u8d56\u7684DNA\u548cRNA\u8131\u9776\uff0c\u800c\u4e14\u5bf9\u4e8e\u80de\u5627\u5576\u7684\u7f16\u8f91\u6548\u7387\u663e\u8457\u63d0\u9ad8\u3002\u4e3a\u4e86\u89e3\u51b3ABE8e\u7684\u7cbe\u51c6\u6027\u95ee\u9898\uff0c\u8be5\u7814\u7a76\u57fa\u4e8eABE8e\u7684\u51b7\u51bb\u7535\u955c\u7ed3\u6784\u8fdb\u884c\u7406\u6027\u8bbe\u8ba1\u548c\u7b5b\u9009\uff0c\u53d1\u73b0\u5728TadA-8e\u8131\u6c28\u9176\u7684\u6d3b\u6027\u53e3\u888b\u5f15\u5165\u5173\u952e\u7a81\u53d8L145T\u548cN108Q\uff08ABE9\uff09\u53ef\u5728\u4fdd\u7559\u9ad8\u7f16\u8f91\u6d3b\u6027\u7684\u540c\u65f6\uff0c\u663e\u8457\u7f29\u5c0f\u7f16\u8f91\u7a97\u53e3\u5230sgRNA\u7684\u7b2c5-6\u4f4d\u7684\u817a\u560c\u5464\uff0c\u6d88\u9664\u5bf9\u80de\u5627\u5576\u7684\u7f16\u8f91\u6d3b\u6027\uff08\u56fe1\uff09\u3002<\/p>\n

\n

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\n

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 <\/p>\n

\n

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\u6df1\u8015\u57fa\u56e0\u6cbb\u7597\u9886\u57df\uff0c\u90a6\u8000\u751f\u7269\u7a81\u7834\u4e0d\u65ad<\/b><\/p>\n

\u90a6\u8000\u751f\u7269\u4f5c\u4e3a\u4e00\u5bb6\u5168\u7403\u6700\u65e9\u8fdb\u884c\u57fa\u56e0\u7f16\u8f91\u6280\u672f\u7814\u53d1\u548c\u5e94\u7528\u7684\u4f01\u4e1a\u4e4b\u4e00\uff0c\u81ea\u6210\u7acb\u4ee5\u6765\u4e00\u76f4\u575a\u6301\u6280\u672f\u521b\u65b0\uff0c\u4e0d\u4ec5\u4e0d\u65ad\u514b\u670d\u884c\u4e1a\u58c1\u5792\u8fdb\u884c\u591a\u7ba1\u7ebf\u6218\u7565\u5e03\u5c40\uff0c\u540c\u65f6\u81f4\u529b\u4e8e\u5f00\u53d1\u56fd\u9645\u9886\u5148\u7684\u57fa\u56e0\u7f16\u8f91\u5de5\u5177\uff0c\u83b7\u5f97\u5177\u6709\u81ea\u4e3b\u77e5\u8bc6\u4ea7\u6743\u7684\u6838\u5fc3\u6280\u672f\u3002\u56de\u9996\u90a6\u8000\u751f\u7269\u7684\u5f00\u62d3\u4e4b\u8def\uff0c\u65e0\u7591\u662f\u4e00\u6bb5\u4e0d\u65ad\u7a81\u7834\u4e0e\u521b\u65b0\u7684\u8fc7\u7a0b\u3002\u76ee\u524d\uff0c\u90a6\u8000\u751f\u7269\u79d1\u5b66\u5bb6\u56e2\u961f\u5728\u57fa\u56e0\u7f16\u8f91\u5de5\u5177\u5f00\u53d1\u3001\u57fa\u56e0\u6cbb\u7597\u5730\u4e2d\u6d77\u8d2b\u8840\u4ee5\u53ca<\/b>CAR-T<\/b>\u6280\u672f\u521b\u65b0\u9886\u57df\uff0c\u5df2\u7ecf\u53d6\u5f97\u5f88\u591a\u91cd\u78c5\u3001\u7a81\u7834\u6027\u8fdb\u5c55\uff1a<\/b><\/p>\n

2019\u5e743\u6708\uff0cNature Medicine<\/i>\u53d1\u6587\uff0c\u53d1\u73b0\u5229\u7528\u57fa\u56e0\u7f16\u8f91\u6280\u672f\u9776\u5411\u7f16\u8f91BCL11A\u7ea2\u7cfb\u589e\u5f3a\u5b50\uff0c\u4f1a\u91cd\u65b0\u5f00\u542f\u03b3\u73e0\u86cb\u767d\u8868\u8fbe\uff0c\u4ee3\u66ff\u6709\u7f3a\u9677\u7684\u03b2\u73e0\u86cb\u767d\uff0c\u6709\u671b\u8fbe\u5230\u6839\u6cbb\u03b2-\u5730\u4e2d\u6d77\u8d2b\u8840\u76ee\u7684\uff1b<\/p>\n

2020\u5e741\u6708\uff0cCell Research<\/i>\u53d1\u6587\uff0c\u7387\u5148\u8bc1\u660e\u5355\u78b1\u57fa\u7f16\u8f91\u5668\u7f16\u8f91\u6280\u672f\u9776\u5411HBG\u542f\u52a8\u5b50\u6fc0\u6d3b\u80ce\u513f\u671f\u8840\u7ea2\u86cb\u767d\u7684\u8868\u8fbe\u5bf9\u4e8e\u6cbb\u7597\u03b2-\u5730\u4e2d\u6d77\u8d2b\u8840\u7684\u53ef\u884c\u6027\u4e0e\u6709\u6548\u6027\uff1b<\/p>\n

2020\u5e743\u6708\uff0cNature Medicine<\/i>\u53d1\u6587\uff0c\u8bc1\u660e\u5355\u78b1\u57fa\u7f16\u8f91\u6280\u672f\u53ef\u4ee5\u9776\u5411BCL11A\u7684\u7ea2\u7cfb\u589e\u5f3a\u5b50\u539f\u4ef6\u6fc0\u6d3b\u80ce\u513f\u671f\u8840\u7ea2\u86cb\u767d\uff0c\u6216\u8005\u7f16\u8f91\u03b2\u8840\u7ea2\u86cb\u767d\u57fa\u56e0\u7684\u7279\u5b9a\u7a81\u53d8\uff0c\u6709\u671b\u901a\u8fc7\u7f16\u8f91\u81ea\u4f53\u9020\u8840\u5e72\u7ec6\u80de\u6cbb\u7597\u5305\u62ec\u03b2-\u5730\u4e2d\u6d77\u8d2b\u8840\u5728\u5185\u7684\u9057\u4f20\u6027\u8840\u6db2\u75be\u75c5\uff1b<\/p>\n

2020\u5e745\u6708\uff0cNature Cell Biology<\/i>\u53d1\u6587\uff0c\u62a5\u9053\u81ea\u4e3b\u7814\u53d1\u7684hyCBEs\u7cfb\u5217\u5de5\u5177\u62e5\u6709\u66f4\u9ad8\u7684\u7f16\u8f91\u6d3b\u6027\u548c\u66f4\u5bbd\u7684\u7f16\u8f91\u7a97\u53e3\uff0c\u5bf9\u4e8e\u03b2\u8840\u7ea2\u86cb\u767d\u75c5\u7684\u6cbb\u7597\u5177\u6709\u66f4\u5927\u7684\u4f18\u52bf\uff1b<\/p>\n

2020\u5e746\u6708\uff0cNature Biotechnology\u53d1\u6587\uff0c\u5f00\u53d1\u4e00\u79cd\u5168\u65b0\u7684\u5177\u6709\u9ad8\u7279\u5f02\u6027\u4e14\u5b89\u5168\u7684\u53cc\u529f\u80fd\u78b1\u57fa\u7f16\u8f91\u5668A\uff06C-BEmax\uff1b<\/p>\n

2022\u5e748\u6708\uff0cNature Medicine<\/i>\u53d1\u6587\uff0c\u516c\u5e03\u4e86\u8be6\u7ec6\u7684\u4e34\u5e8a\u6570\u636e\uff0c\u90a6\u8000\u751f\u7269BRL-101\u57fa\u56e0\u6cbb\u7597\u5730\u4e2d\u6d77\u8d2b\u8840\u75c7\u60a3\u513f\u8131\u79bb\u8f93\u8840\u4f9d\u8d56\u5df2\u8d85\u8fc72\u5e74\uff0c\u5e76\u66f4\u4e3a\u5168\u9762\u5730\u89e3\u8bfb\u4e86BRL-101\u6cbb\u7597\u60a3\u8005\u7684\u7597\u6548\u548c\u5b89\u5168\u6027\u7279\u5f81\uff1b<\/p>\n

2022\u5e748\u6708\uff0cNature<\/i>\u53d1\u6587\uff0c\u8bc1\u660e\u4e86\u90a6\u8000\u751f\u7269BRL-201\u975e\u75c5\u6bd2PD1\u5b9a\u70b9\u6574\u5408CAR-T\u7597\u6cd5\u51fa\u8272\u7684\u4e34\u5e8a\u5b89\u5168\u6027\u548c\u6709\u6548\u6027\uff0c\u4f7fNHL\u60a3\u8005\u65e0\u764c\u751f\u5b58\u671f\u6700\u957f\u8d85\u8fc72\u5e74\u3002<\/p>\n

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\u4e0a\u6d772022\u5e7410\u670815\u65e5 \/\u7f8e\u901a\u793e\/ — \u78b1\u57fa\u7f16\u8f91\u6280\u672f\u6700\u65e9\u7531\u54c8\u4f5b\u5927\u5b66David R. 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