{"id":77668,"date":"2017-12-13T17:01:49","date_gmt":"2017-12-13T09:01:49","guid":{"rendered":"http:\/\/highscope.ch.ntu.edu.tw\/wordpress\/?p=77668"},"modified":"2021-10-06T16:03:36","modified_gmt":"2021-10-06T08:03:36","slug":"%e4%bd%bf%e7%94%a8-crispr-%e6%8a%80%e8%a1%93%e6%b8%85%e9%99%a4%e9%ab%94%e5%85%a7%e7%9a%84%e6%84%9b%e6%bb%8b%e7%97%85%e7%97%85%e6%af%92","status":"publish","type":"post","link":"http:\/\/localhost\/%e4%bd%bf%e7%94%a8-crispr-%e6%8a%80%e8%a1%93%e6%b8%85%e9%99%a4%e9%ab%94%e5%85%a7%e7%9a%84%e6%84%9b%e6%bb%8b%e7%97%85%e7%97%85%e6%af%92\/","title":{"rendered":"\u4f7f\u7528 CRISPR \u6280\u8853\u6e05\u9664\u9ad4\u5167\u7684\u611b\u6ecb\u75c5\u75c5\u6bd2"},"content":{"rendered":"<div class=\"pf-content\"><p><span style=\"color: #ff6600;\"><strong>\u4f7f\u7528 CRISPR \u6280\u8853\u6e05\u9664\u9ad4\u5167\u7684\u611b\u6ecb\u75c5\u75c5\u6bd2<\/strong><\/span><br \/>\n<span style=\"color: #008000;\"><strong>\u5fb7\u5dde\u5927\u5b78\u5206\u5b50\u751f\u7269\u79d1\u5b78\u7814\u7a76\u6240\u99ac\u5343\u60e0\/<\/strong><\/span><span style=\"color: #008000;\"><strong>\u570b\u7acb\u81fa\u7063\u5927\u5b78\u751f\u547d\u79d1\u5b78\u7cfb\u9673\u4fca\u5b8f\u6559\u6388\u8cac\u4efb\u7de8\u8f2f<\/strong><\/span><\/p>\n<p>\u904e\u53bb\u56db\u5e74\u4f86CRISPR\/Cas9\u57fa\u56e0\u7de8\u8f2f\u6280\u8853\uff0c\u88ab\u5ee3\u6cdb\u4f7f\u7528\u65bc\u57fa\u790e\u79d1\u5b78\u4ee5\u53ca\u81e8\u5e8a\u524d\u5be6\u9a57\u3002Cas9 \u9175\u7d20\u5728\u5f15\u5c0eRNA (guide RNA) \u5e8f\u5217\u5e36\u9818\u4e0b\uff0c\u53ef\u4ee5\u5207\u65b7\u7279\u5b9a\u7684\u57fa\u56e0\u4f4d\u7f6e\uff0c\u9020\u6210\u53cc\u80a1 DNA\u7684\u65b7\u88c2\uff0c\u7d30\u80de\u5075\u6e2c\u5230\u53d7\u640d\u7684DNA\u6703\u8d77\u52d5\u4fee\u88dc\u6a5f\u5236\uff0c\u53ef\u4ee5\u5927\u5e45\u63d0\u9ad8\u57fa\u56e0\u540c\u6e90\u91cd\u7d44\u7684\u6548\u7387\uff0c\u4f7f\u5f97\u7de8\u8f2f\u5404\u7a2e\u7d30\u80de\u548c\u5668\u5b98\u7684\u57fa\u56e0\u8b8a\u5f97\u5bb9\u6613\u4e14\u5feb\u901f\u3002\u5728\u91ab\u5b78\u7814\u7a76\u4e0a\uff0c\u79d1\u5b78\u5bb6\u5011\u81f4\u529b\u65bc\u61c9\u7528\u6b64\u6280\u8853\u4f86\u767c\u5c55\u5177\u6709\u6f5b\u80fd\u7684\u6cbb\u7642\u65b9\u5f0f\uff0c\u5305\u62ec\u6cbb\u7642\u907a\u50b3\u75be\u75c5\u3001\u764c\u75c7\u4ee5\u53ca\u611f\u67d3\u6027\u75be\u75c5\u7b49(1,2)\u3002<!--more--><\/p>\n<p>\u611b\u6ecb\u75c5\u7684\u75c5\u539f\u9ad4\u662f\u4eba\u985e\u514d\u75ab\u7f3a\u9677\u75c5\u6bd2\uff08Human Immunodeficiency Virus, HIV-1\uff09\uff0c\u76ee\u524d\u4ecd\u6301\u7e8c\u5371\u5bb3\u5927\u773e\u7684\u5065\u5eb7\uff0c\u5168\u7403\u6709\u8d85\u904e\u56db\u5343\u842c\u7684\u4eba\u611f\u67d3\u611b\u6ecb\u75c5\uff0c\u800c\u4e14\u6bcf\u5e74\u4ee5\u591a\u65bc\u5169\u767e\u842c\u4eba\u611f\u67d3\u7684\u901f\u5ea6\u589e\u52a0\u4e2d\u3002\u76ee\u524d\u5ee3\u6cdb\u4f7f\u7528\u4fd7\u7a31\u300c\u96de\u5c3e\u9152\u7642\u6cd5\u300d\u7684\u806f\u5408\u53cd\u8f49\u9304\u75c5\u6bd2\u7642\u6cd5(Combination antiretroviral therapy, cART) \u4f86\u6291\u5236\u6d3b\u8e8d\u7684\u75c5\u6bd2\u8907\u88fd\uff0c\u6e1b\u7de9\u75c5\u60c5\u7684\u767c\u5c55\uff0c\u964d\u4f4e\u767c\u75c5\u7387\u548c\u6b7b\u4ea1\u7387\uff0c\u4f46\u662f\u4ecd\u7136\u6c92\u6709\u8fa6\u6cd5\u75ca\u7652\uff0c\u800c\u4e14\u4e00\u65e6\u505c\u6b62\u7528\u85e5\uff0c\u75c5\u6bd2\u6703\u81ea\u884c\u958b\u59cb\u8907\u88fd\uff0c\u9020\u6210\u75c5\u60c5\u60e1\u5316\u3002\u5176\u4e3b\u8981\u539f\u56e0\u662f HIV-1\u75c5\u6bd2\u5177\u6709\u8eb2\u907f\u4e26\u4e14\u9577\u671f\u6f5b\u4f0f\u5728\u9ad4\u5167\u7684\u7279\u6027\uff0cHIV-1\u75c5\u6bd2\u6703\u5f9e\u5176\u55ae\u80a1RNA\u53cd\u8f49\u9304\u51fa\u96d9\u80a1DNA\uff0c\u4e26\u4e14\u5d4c\u5165\u75c5\u4eba\u57fa\u56e0\u9ad4\u5167\uff0c\u4f7f\u514d\u75ab\u7cfb\u7d71\u7121\u6cd5\u5bdf\u89ba\uff0c\u975e\u5e38\u96e3\u5f9e\u75c5\u4eba\u9ad4\u5167\u5b8c\u5168\u6e05\u9664\u4e7e\u6de8\u3002\u7f8e\u570b\u5929\u666e\u5927\u5b78\u8def\u6613\u65af\u5361\u8332\u91ab\u5b78\u9662 (Lewis Katz School of Medicine at Temple University) \u548c\u5339\u8332\u5821\u5927\u5b78\u7814\u7a76\u5718\u968a\u7684\u6700\u65b0\u7814\u7a76\u6210\u679c\uff0c\u6709\u4e86\u7a81\u7834\u6027\u7684\u767c\u5c55\u3002\u7814\u7a76\u986f\u793a\u5229\u7528 CRISPR\/Cas9 \u6280\u8853\uff0c\u53ef\u4ee5\u6709\u6548\u5730\u5c07\u6f5b\u4f0f\u5728\u52d5\u7269DNA\u4e2d\u7684 HIV-1 \u75c5\u6bd2\u57fa\u56e0\u79fb\u9664\uff0c\u53bb\u9664\u5f8c\u7e8c\u611f\u67d3\u7684\u72c0\u6cc1\u3002\u6b64\u7814\u7a76\u5718\u968a\u6700\u5148\u4ee5\u4e09\u7a2e\u5be6\u9a57\u52d5\u7269\uff0c\u4f86\u9032\u884c\u6b64\u58ef\u8209\u5be6\u9a57\u7684\u5718\u968a\u3002\u7814\u7a76\u6210\u679c\u65bc2017\u5e74\u4e94\u6708\u521d\u520a\u767b\u65bcMolecular Therapy\u671f\u520a (1)\u3002<\/p>\n<p>\u5ef6\u7e8c\u8a72\u7814\u7a76\u5718\u968a\u65bc 2016\u5e74\u767c\u8868\u7684\u8ad6\u6587\uff0c\u7576\u6642\u6210\u529f\u5730\u5c07\u5927\u90e8\u5206\u5d4c\u5728\u57fa\u56e0\u8f49\u6b96\u5927\u9f20\u53ca\u8001\u9f20\u5668\u5b98\u7d44\u7e54\u7684 HIV-1\u75c5\u6bd2\u57fa\u56e0\u7247\u6bb5\u79fb\u9664\u6389\u3002\u65b0\u7684\u7814\u7a76\u7d50\u679c\u5247\u66f4\u52a0\u660e\u78ba\uff0c\u800c\u4e14\u7d93\u904e\u6539\u826f\u7684CRISPR\/Cas9\u7cfb\u7d71\u6548\u7387\u66f4\u9ad8\uff0c\u66f4\u6210\u529f\u5730\u4f7f\u7528\u65bc\u4e09\u7a2e\u6d3b\u9ad4\u5be6\u9a57\u52d5\u7269\u4e2d\u3002\u7814\u7a76\u4eba\u54e1\u4f7f\u7528\u817a\u76f8\u95dc\u75c5\u6bd2(AAV) \u8f09\u9ad4\u8f38\u9001\u7cfb\u7d71\uff0c\u9078\u64c7AAV-DJ \u548cAAV-DJ\/8\u5169\u7a2e\u8f09\u9ad4\uff0c\u53ef\u4ee5\u50b3\u9001\u81f3\u66f4\u591a\u7a2e\u7d44\u7e54\u548c\u5668\u5b98\uff0c\u540c\u6642\u627f\u8f09\u56db\u7a2e\u4e0d\u540c\u7684\u5f15\u5c0e RNA\u8f49\u9304\u55ae\u4f4d\uff0c\u4ee5\u53ca\u4f86\u81ea\u83cc\u7a2e <em>Saphylococcus aureus<\/em> \u6bd4\u8f03\u5c0f\u7684Cas9 (\u7c21\u7a31\u70ba saCas9)\u57fa\u56e0\uff0c\u5c07\u6b64\u57fa\u56e0\u7de8\u8f2f\u8f09\u9ad4\u4ee5\u975c\u8108\u6ce8\u5c04\u7684\u65b9\u6cd5\u6253\u5165\u8001\u9f20\u9ad4\u5167\uff0c\u518d\u9001\u5230\u4e0d\u540c\u7684\u6a19\u7684\u7d30\u80de\u3002\u7814\u7a76\u4eba\u54e1\u6210\u529f\u5730\u5c07\u57fa\u56e0\u8f49\u6b96\u8001\u9f20 (HIV-1 Tg26 trangenic mouse) \u57fa\u56e0\u9ad4\u5167\u7684 HIV-1 DNA \u5207\u65b7\u79fb\u9664\uff0c\u6e1b\u5c11\u75c5\u6bd2\u57fa\u56e0\u5927\u7d04 60\u5230 95%\u7684 RNA\u8868\u73fe\u91cf\uff0c\u9032\u4e00\u6b65\u8b49\u5be6\u4ed6\u5011\u5148\u524d\u7684\u7814\u7a76\u7d50\u679c\u3002\u53e6\u5916\u5c07\u6b64\u7cfb\u7d71\u9001\u5165\u5169\u7a2e\u4e0d\u540c\u7684\u5be6\u9a57\u8001\u9f20\u4e5f\u540c\u6a23\u53ef\u884c\uff0c\u5176\u4e2d\u4e00\u7a2e\u5be6\u9a57\u8001\u9f20\u662f\u611f\u67d3 EcoHIV \u75c5\u6bd2(\u76f8\u7576\u65bc\u4eba\u985e\u7684 HIV-1\u75c5\u6bd2\uff09\uff0c\u6b63\u8655\u65bc\u6025\u6027\u611f\u67d3\u7684\u72c0\u6cc1\uff0c\u4ed6\u5011\u6210\u529f\u5730\u4ee5\u6b64\u6280\u8853\u963b\u65b7\u75c5\u6bd2\u8907\u88fd\uff0c\u9032\u800c\u9810\u9632\u7cfb\u7d71\u611f\u67d3\u3002\u6e05\u9664\u75c5\u6bd2\u7684\u6548\u7387\u5728\u809d\u7d30\u80de\u53ef\u9054\u5230 96%\uff0c\u8b49\u660e\u53ef\u4ee5\u7528CRISPR\/Cas9\u7cfb\u7d71\u9032\u884c\u9810\u9632\u6027\u6cbb\u7642\u4e26\u4e14\u6839\u9664\u75c5\u6bd2\u3002\u7b2c\u4e09\u7a2e\u5be6\u9a57\u52d5\u7269\u662f\u79fb\u690d\u6709\u4eba\u985e\u7d30\u80de\u65bc\u5404\u500b\u7d44\u7e54\u5668\u5b98\u7684\u4eba\u985e\u5316\u8001\u9f20(BLT mice)\uff0c\u540c\u6642\u611f\u67d3HIV-1\u75c5\u6bd2\uff0c\u8655\u65bc\u9577\u671f\u6f5b\u4f0f\u611f\u67d3\u72c0\u6cc1\u3002\u4ee4\u4eba\u9a5a\u5606\u7684\u662f\uff0c\u50c5\u50c5\u4e00\u6b21\u6cbb\u7642\uff0c\u5373\u6210\u529f\u5730\u5c07\u6f5b\u4f0f\u5728\u4e0d\u540c\u7d44\u7e54\u5668\u5b98\u5167\u7684\u75c5\u6bd2\u57fa\u56e0\u7247\u65b7\u79fb\u9664\u3002<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"size-full wp-image-77669 aligncenter\" src=\"http:\/\/highscope.ch.ntu.edu.tw\/wordpress\/wp-content\/uploads\/2017\/12\/\u611b\u6ecb\u75c5\uff3f\u8001\u9f20.jpg\" alt=\"\" width=\"415\" height=\"322\" \/><\/p>\n<p style=\"text-align: center;\">\u5716\uff1a\u79fb\u9664\u5927\u90e8\u5206\u5d4c\u5728\u57fa\u56e0\u8f49\u6b96\u5927\u9f20\u53ca\u8001\u9f20\u5668\u5b98\u7d44\u7e54\u7684 HIV-1\u75c5\u6bd2\u57fa\u56e0\u7247\u6bb5\u5be6\u9a57<\/p>\n<p style=\"text-align: center;\">\uff08\u5716\u7247\u4f86\u6e90\uff1aMolecular Therapy 2017, 25(5), 1063.\uff09<\/p>\n<p>\u70ba\u4e86\u5224\u65b7\u9019\u7b56\u7565\u662f\u5426\u6210\u529f\uff0c\u7814\u7a76\u5718\u968a\u6e2c\u91cfHIV-1\u75c5\u6bd2\u7684 RNA\u8868\u73fe\u91cf\uff0c\u540c\u6642\u4f7f\u7528\u7531Won-Bin Young \u535a\u58eb\u65b0\u958b\u767c\u7684\u6d3b\u9ad4\u751f\u7269\u767c\u5149\u5f71\u50cf\u7cfb\u7d71\uff0c\u6e96\u78ba\u5730\u986f\u793a\u53d7HIV-1 \u611f\u67d3\u7684\u7d30\u80de\u5728\u52d5\u7269\u9ad4\u5167\u5206\u4f48\u7684\u4f4d\u7f6e\u548c\u5b58\u5728\u7684\u6642\u9593\uff0c\u8b93\u7814\u7a76\u4eba\u54e1\u53ef\u4ee5\u540c\u6b65\u89c0\u5bdf\u75c5\u6bd2\u8907\u88fd\u4ee5\u53ca\u5176\u6f5b\u4f0f\u5728\u53d7\u611f\u67d3\u7d30\u80de\u548c\u7d44\u7e54\u7684\u60c5\u6cc1\u3002\u6bd4\u8f03\u6cbb\u7642\u7d44\u548c\u5c0d\u7167\u7d44\uff0c\u53ef\u4ee5\u770b\u5230\u7d93\u7531 CRISPR\/Cas9 \u6cbb\u7642\u7684\u8001\u9f20\u5176\u75c5\u6bd2\u6307\u6a19\u660e\u986f\u6e1b\u5c11\uff0c\u8868\u793a\u7b56\u7565\u6210\u529f!<\/p>\n<p>\u7e3d\u7d50\u4f86\u8aaa\uff0c\u65b0\u7684\u6cbb\u7642\u65b9\u5f0f\u4ee5\u817a\u76f8\u95dc\u75c5\u6bd2\uff08AAV) \u70ba\u904b\u9001\u7cfb\u7d71\uff0c\u5c07\u6539\u826f\u904e\u5305\u542b\u6709\u56db\u7a2e\u5f15\u5c0e RNA\u53ca saCas9\u7684\u57fa\u56e0\u7de8\u8f2f\u8f09\u9ad4\uff0c\u6210\u529f\u5730\u904b\u9001\u81f3\u5404\u500b\u7ec4\u7e54\u5668\u5b98\uff0c\u9032\u800c\u6709\u6548\u5730\u79fb\u9664\u5d4c\u5728\u5bc4\u4e3b\u7d30\u80de\u57fa\u56e0\u9ad4\u5167\u7684 HIV-1\u75c5\u6bd2\u57fa\u56e0\u3002\u907f\u514d\u75c5\u6bd2\u4ee5\u7a81\u8b8a\u65b9\u5f0f\u8eb2\u6389\u5075\u6e2c\uff0c\u9054\u5230\u5b8c\u5168\u7684\u6cbb\u7642\u6548\u679c\u3002<\/p>\n<p>\u7814\u7a76\u5718\u968a\u5c0d\u4ed6\u5011\u7684\u7814\u7a76\u767c\u73fe\u611f\u5230\u8208\u596e\uff0c\u4e5f\u5c0d\u4e0b\u4e00\u6b65\u7684\u7814\u7a76\u8868\u793a\u6a02\u89c0\u3002\u4e0b\u4e00\u500b\u968e\u6bb5\u5c07\u662f\u5728\u9748\u9577\u985e\u52d5\u7269\u91cd\u8907\u6574\u500b\u5be6\u9a57\u904e\u7a0b\uff0c\u53ef\u4ee5\u66f4\u52a0\u4e86\u89e3\u53bb\u9664\u75c5\u6bd2\u7684\u72c0\u6cc1\uff0c\u4e26\u4e14\u4e86\u89e3\u75c5\u7665\u7684\u6f14\u8b8a\u3002\u6700\u7d42\u76ee\u6a19\u662f\u5728\u81e8\u5e8a\u4e0a\u904b\u7528\u5230\u75c5\u4eba\u8eab\u4e0a\uff0c\u7d66\u4e88\u611b\u6ecb\u75c5\u60a3\u5b8c\u5168\u75ca\u7652\u7684\u6cbb\u7642 \u3002<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p>\u53c3\u8003\u6587\u737b:<\/p>\n<ol>\n<li>\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Yin, C., Zhang, T., Qu, X., Zhang, Y., Putatunda, R., Xiao, X., Li, F., Xiao, W., Zhao, H., Dai, S.<em> et al.<\/em> (2017) In Vivo Excision of HIV-1 Provirus by saCas9 and Multiplex Single-Guide RNAs in Animal Models. <em>Molecular therapy : the journal of the American Society of Gene Therapy<\/em>, <strong>25<\/strong>, 1168-1186.<\/li>\n<li>\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Kaminski, R., Bella, R., Yin, C., Otte, J., Ferrante, P., Gendelman, H.E., Li, H., Booze, R., Gordon, J., Hu, W.<em> et al.<\/em> (2016) Excision of HIV-1 DNA by gene editing: a proof-of-concept in vivo study. <em>Gene therapy<\/em>, <strong>23<\/strong>, 696.<\/li>\n<\/ol>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>\u4f7f\u7528 CRISPR \u6280\u8853\u6e05\u9664\u9ad4\u5167\u7684\u611b\u6ecb\u75c5\u75c5\u6bd2 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