{"id":230242,"date":"2021-12-07T06:30:01","date_gmt":"2021-12-06T22:30:01","guid":{"rendered":"\/\/m.iemloyee.com\/?p=230242"},"modified":"2021-12-06T17:47:12","modified_gmt":"2021-12-06T09:47:12","slug":"%e4%bf%84%e4%ba%a5%e4%bf%84%e5%b7%9e%e7%ab%8b%e5%a4%a7%e5%ad%a6%e8%91%a3%e4%b8%80%e6%b4%b2%e5%9b%a2%e9%98%9facc-chem-res-%ef%bc%9a%e7%94%a8%e4%ba%8e%e6%b2%bb%e7%96%97%e7%9a%84%e8%84%82%e8%b4%a8","status":"publish","type":"post","link":"\/\/m.iemloyee.com\/?p=230242","title":{"rendered":"\u4fc4\u4ea5\u4fc4\u5dde\u7acb\u5927\u5b66\u8463\u4e00\u6d32\u56e2\u961fAcc. Chem. Res.\uff1a\u7528\u4e8e\u6cbb\u7597\u7684\u8102\u8d28\u7eb3\u7c73\u9897\u7c92mRNA\u5236\u5242"},"content":{"rendered":"<p><strong>\u3010\u5f15\u8a00\u3011<\/strong><\/p>\n<p>\u7ecf\u8fc7\u51e0\u5341\u5e74\u7684\u5e7f\u6cdb\u57fa\u7840\u7814\u7a76\u548c\u4e34\u5e8a\u8bd5\u9a8c\uff0c\u8102\u8d28\u7eb3\u7c73\u9897\u7c92\uff08LNPs\uff09\u5df2\u7ecf\u8bc1\u660e\u4e86\u6709\u6548\u7684mRNA\u4f20\u9012\uff0c\u5982Moderna\u548cPfizer-BioNTech\u7684\u6297COVID-19\u75ab\u82d7\u3002\u6b64\u5916\uff0c\u7814\u7a76\u4eba\u5458\u548c\u4e34\u5e8a\u533b\u751f\u4e00\u76f4\u5728\u7814\u7a76\u5404\u79cd\u6cbb\u7597\u9002\u5e94\u75c7\u7684mRNA\u7597\u6cd5\uff0c\u5305\u62ec\u86cb\u767d\u8d28\u66ff\u4ee3\u7597\u6cd5\u3001\u57fa\u56e0\u7ec4\u7f16\u8f91\u548c\u764c\u75c7\u514d\u75ab\u7597\u6cd5\u3002\u5728\u4e34\u5e8a\u5b9e\u8df5\u4e2d\u5b9e\u73b0\u8fd9\u4e9b\u7597\u6cd5\u8fd8\u9762\u4e34\u7740\u8bb8\u591a\u8270\u5de8\u7684\u6311\u6218\u3002\u9996\u5148\uff0c\u9700\u8981\u9488\u5bf9\u4e0d\u540c\u7684\u7ec6\u80de\u7c7b\u578b\u5f00\u53d1\u65b0\u578b\u7684\u4f20\u8f93\u7cfb\u7edf\uff0c\u5982\u9ad8\u9012\u9001\u6548\u7387\u548c\u4f4e\u6bd2\u6027LNPs\u3002\u5176\u6b21\uff0cmRNA\u5206\u5b50\u9700\u8981\u88ab\u8bbe\u8ba1\u6765\u6539\u5584\u836f\u7269\u6027\u80fd\u3002\u6700\u540e\uff0cLNP-mRNA\u7eb3\u7c73\u9897\u7c92\u5236\u5242\u9700\u8981\u4e0e\u5176\u6cbb\u7597\u5e94\u7528\u76f8\u5339\u914d\u3002<\/p>\n<p><strong>\u3010\u6210\u679c\u7b80\u4ecb\u3011<\/strong><\/p>\n<p>\u8fd1\u65e5\uff0c<strong><b>\u4fc4\u4ea5\u4fc4\u5dde\u7acb\u5927\u5b66\u8463\u4e00\u6d32\u6559\u6388<\/b><\/strong>\u56e2\u961f\u603b\u7ed3\u4e86\u5728\u8bbe\u8ba1\u548c\u5f00\u53d1\u5404\u79cd\u7c7b\u578b\u7684\u8102\u7c7b\u53ca\u5176\u884d\u751f\u7269\u65b9\u9762\u7684\u6700\u65b0\u8fdb\u5c55\uff0c\u8fd9\u4e9b\u8102\u7c7b\u5316\u5408\u7269\u53ef\u4ee5\u7531\u591a\u79cd\u7c7b\u578b\u7684mRNA\u5206\u5b50\u7ec4\u6210\uff0c\u7528\u4e8e\u6cbb\u7597\u591a\u79cd\u75be\u75c5\u3002\u4f8b\u5982\uff0c\u8bbe\u60f3\u4e86\u4e00\u7cfb\u5217\u57fa\u4e8e\u82ef\u6838\u3001\u9170\u80fa\u8fde\u63a5\u5242\u548c\u758f\u6c34\u5c3e\u90e8\u7ed3\u6784\u7684\u53ef\u7535\u79bb\u7c7b\u8102\u5206\u5b50\u3002\u53d1\u73b0N<sup>1<\/sup>,N<sup>3<\/sup>,N<sup>5<\/sup>-\u4e09(3-(\u53cc\u5341\u4e8c\u70f7\u57fa\u6c28\u57fa)\u4e19\u57fa)\u82ef-1,3,5-\u4e09\u7532\u9170\u80fa(TT3)\u662f\u4f53\u5916\u548c\u4f53\u5185\u4f20\u9012mRNA\u7684\u5148\u5bfc\u5316\u5408\u7269\u3002\u800c\u4e14\uff0c\u901a\u8fc7\u5f15\u5165\u652f\u5316\u916f\u6216\u76f4\u94fe\u916f\u94fe\u53ef\u4ee5\u6765\u8c03\u8282\u8fd9\u4e9b\u7c7b\u8102\u5206\u5b50\u7684\u751f\u7269\u964d\u89e3\u6027\u3002\u53e6\u4e00\u65b9\u9762\uff0c\u5728\u4eff\u751f\u5316\u5408\u7269\u7684\u542f\u53d1\u4e0b\uff0c\u8be5\u56e2\u961f\u5408\u6210\u4e86\u7ef4\u751f\u7d20\u884d\u751f\u7684\u8102\u7c7b\u3001\u5316\u7597\u836f\u7269\u884d\u751f\u7684\u8102\u7c7b\u3001\u78f7\u8102\u7c7b\u4ee5\u53ca\u7cd6\u8102\u7c7b\u5316\u5408\u7269\u3002\u8fd9\u4e9b\u5206\u5b50\u6781\u5927\u5730\u62d3\u5bbd\u4e86mRNA\u4f20\u9012\u7684\u53ef\u7535\u79bb\u8102\u8d28\u7684\u5316\u5b66\u7a7a\u95f4\u3002\u5728\u53e6\u4e00\u90e8\u5206\uff0c\u4f5c\u8005\u7740\u91cd\u4ecb\u7ecd\u4e86\u5728mRNA\u5de5\u7a0b\u7814\u7a76\u65b9\u5411\u4e0a\u7684\u52aa\u529b\u3002\u5316\u5b66\u4fee\u9970\u7684\u6838\u82f7\u9178\u53ef\u4ee5\u4f18\u5316\u4e86mRNA\u7684\u5316\u5b66\u7ed3\u6784\uff0c\u4ee5\u589e\u52a0\u86cb\u767d\u8d28\u7684\u8868\u8fbe\uff0c\u5982\u4f2a\u5c3f\u5627\u5576(\u03c8)\uff0c 5-\u7532\u6c27\u57fa\u5c3f\u5627\u5576(5moU)\uff0c\u548cN<sup>1<\/sup>\u00a0-\u7532\u57fa\u4f2a\u5c3f\u5627\u5576(me<sup>1<\/sup>\u03c8)\u3002\u6b64\u5916\uff0c\u8fd8\u8bbe\u8ba1\u4e86mRNA 5\u2019\u975e\u7ffb\u8bd1\u533a\u57df(5\u2019- UTR)\u548c3\u2019\u975e\u7ffb\u8bd1\u533a\u57df(3\u2019- UTR)\u7684\u5e8f\u5217\uff0c\u663e\u8457\u63d0\u9ad8\u4e86\u86cb\u767d\u8d28\u8868\u8fbe\u3002\u968f\u7740LNP\u7684\u5f00\u53d1\u548cmRNA\u5de5\u7a0b\u7684\u8fdb\u5c55\uff0c\u8fd9\u4e9b\u6280\u672f\u5c06\u5e94\u7528\u4e8e\u9057\u4f20\u75c5\u3001\u4f20\u67d3\u75c5\u3001\u764c\u75c7\u7b49\u75be\u75c5\u7684\u6cbb\u7597\u3002\u4f8b\u5982\uff0cTT3\u53ca\u5176\u7c7b\u4f3c\u7269\u884d\u751f\u7684\u7c7b\u8102\u7eb3\u7c73\u9897\u7c92\u53ef\u4ee5\u6709\u6548\u5730\u4f20\u9012\u51dd\u8840\u56e0\u5b50IX\u6216VIII mRNA\uff0c\u5e76\u6062\u590d\u8840\u53cb\u75c5\u5c0f\u9f20\u6a21\u578b\u7684\u51dd\u8840\u6d3b\u6027\u3002\u7f16\u7801SARS-CoV-2\u6297\u539f\u7684mRNA\u53ef\u4f5c\u4e3a\u65b0\u578b\u51a0\u72b6\u75c5\u6bd2\u80ba\u708e\u7684\u5019\u9009\u75ab\u82d7\u3002\u542b\u6709\u6297\u83cc\u80bd\u7ec4\u7ec7\u86cb\u767d\u9176B mRNA\u7684\u7ef4\u751f\u7d20\u8102\u8d28\u7eb3\u7c73\u9897\u7c92\u80fd\u591f\u52a0\u5f3a\u5de8\u566c\u7ec6\u80de\u8f6c\u79fb\u6765\u6cbb\u7597\u591a\u836f\u8010\u836f\u7ec6\u83cc\u8d25\u8840\u75c7\u3002\u7f16\u7801\u5171\u523a\u6fc0\u53d7\u4f53\u7684mRNA\u7684\u78f7\u8102\u7b49\u4eff\u751f\u8102\u7c7b\u53ef\u589e\u5f3a\u764c\u75c7\u514d\u75ab\u6cbb\u7597\u3002\u8be5\u7efc\u8ff0\u4ee5\u9898\u4e3a<strong><b>\u201cLipid Nanoparticle\u2013mRNA Formulations for Therapeutic Applications\u201d<\/b><\/strong>\u53d1\u8868\u5728\u4e86<strong><b>Acc. Chem. Res.<\/b><\/strong>\u4e0a\u3002<img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-230244\" src=\"\/\/m.iemloyee.com\/wp-content\/uploads\/2021\/11\/0-13.jpg\" alt=\"\" width=\"600\" height=\"226\" srcset=\"\/\/m.iemloyee.com\/wp-content\/uploads\/2021\/11\/0-13.jpg 600w, \/\/m.iemloyee.com\/wp-content\/uploads\/2021\/11\/0-13-300x113.jpg 300w\" sizes=\"(max-width: 600px) 100vw, 600px\" \/><\/p>\n<p><strong>\u3010\u56fe\u6587\u5bfc\u8bfb\u3011<\/strong><\/p>\n<p><strong>\u56fe<\/strong><strong>1 FTT5\u548cFTT9 LLN\u7684\u751f\u7269\u964d\u89e3\u6027<\/strong><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-230245\" src=\"\/\/m.iemloyee.com\/wp-content\/uploads\/2021\/11\/1-16.jpg\" alt=\"\" width=\"600\" height=\"133\" srcset=\"\/\/m.iemloyee.com\/wp-content\/uploads\/2021\/11\/1-16.jpg 600w, \/\/m.iemloyee.com\/wp-content\/uploads\/2021\/11\/1-16-300x67.jpg 300w\" sizes=\"(max-width: 600px) 100vw, 600px\" \/><\/p>\n<p>(A) FTT5\u548c(B) FTT9\u5728\u4f53\u5185\u7684\u751f\u7269\u964d\u89e3\u6027\u3002<\/p>\n<p>(C,D)\u9759\u8109\u6ce8\u5c04FTT5-hFIX mRNA\u540e\u8840\u53cb\u75c5A\u5c0f\u9f20\u7684(C)\u51dd\u8840\u56e0\u5b50VIII\u6c34\u5e73\u548c(D)\u6d3b\u6027\u3002<\/p>\n<p><strong>\u56fe<\/strong><strong>2 \u53ef\u7535\u79bb\u7684\u8102\u8d28<\/strong><strong>&#8211;<\/strong><strong>mRNA<\/strong><strong>\u5236\u5242<\/strong><strong>\u4f5c\u4e3aCOVID-19\u75ab\u82d7<\/strong><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-230246\" src=\"\/\/m.iemloyee.com\/wp-content\/uploads\/2021\/11\/2-15.jpg\" alt=\"\" width=\"600\" height=\"170\" srcset=\"\/\/m.iemloyee.com\/wp-content\/uploads\/2021\/11\/2-15.jpg 600w, \/\/m.iemloyee.com\/wp-content\/uploads\/2021\/11\/2-15-300x85.jpg 300w\" sizes=\"(max-width: 600px) 100vw, 600px\" \/><\/p>\n<p>(A) mRNA UTR\u4f18\u5316\u53ca\u5176\u5728COVID-19 mRNA\u75ab\u82d7\u4e2d\u7684\u5e94\u7528\u8bf4\u660e\u3002<\/p>\n<p>(B)\u808c\u8089\u6ce8\u5c04\u540e\u5c0f\u9f20\u8840\u6e05IgG\u6c34\u5e73\u3002<\/p>\n<p>(C) TT3-NASAR mRNA\u5236\u5242\u4f5c\u4e3aCOVID-19 mRNA\u75ab\u82d7\u7684\u5242\u91cf\u6548\u5e94\u3002<\/p>\n<p><strong>\u56fe<\/strong><strong>3 mRNA\u7eb3\u7c73\u7c92\u5b50<\/strong><strong>\u5236\u5242<\/strong><strong>\u6cbb\u7597\u7ec6\u83cc\u611f\u67d3<\/strong><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-230247\" src=\"\/\/m.iemloyee.com\/wp-content\/uploads\/2021\/11\/3-15.jpg\" alt=\"\" width=\"600\" height=\"136\" srcset=\"\/\/m.iemloyee.com\/wp-content\/uploads\/2021\/11\/3-15.jpg 600w, \/\/m.iemloyee.com\/wp-content\/uploads\/2021\/11\/3-15-300x68.jpg 300w\" sizes=\"(max-width: 600px) 100vw, 600px\" \/><\/p>\n<p>(A)\u542b\u6709\u4e0e\u6eb6\u9176\u4f53\u4e2d\u7684\u7ec4\u7ec7\u86cb\u767d\u9176B\u8fde\u63a5\u7684\u6297\u83cc\u80bd\u7684\u5de8\u566c\u7ec6\u80de\uff08MACs\uff09\u6cbb\u7597\u8010\u591a\u836f\u7ec6\u83cc\u8d25\u8840\u75c7\u7684\u56fe\u89e3\uff1a(i)\u8fc7\u7ee7\u6027\u5de8\u566c\u7ec6\u80de\u6cbb\u7597\uff1b(ii)\u5c0f\u9f20\u4ece\u8010\u591a\u836f\u7ec6\u83cc\u8bf1\u53d1\u7684\u8d25\u8840\u75c7\u4e2d\u6062\u590d\u3002<\/p>\n<p>(B,C)\u6cbb\u7597\u540e\u8d25\u8840\u75c7\u5c0f\u9f20\u7684(B)\u5b58\u6d3b\u7387\u548c(C)\u4f53\u91cd\u3002<\/p>\n<p><strong>\u56fe<\/strong><strong>4 A20\u5c0f\u9f20\u80bf\u7624\u6a21\u578b\u7684\u6cbb\u7597\u6548\u679c<\/strong><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-230248\" src=\"\/\/m.iemloyee.com\/wp-content\/uploads\/2021\/11\/4-12.jpg\" alt=\"\" width=\"600\" height=\"130\" srcset=\"\/\/m.iemloyee.com\/wp-content\/uploads\/2021\/11\/4-12.jpg 600w, \/\/m.iemloyee.com\/wp-content\/uploads\/2021\/11\/4-12-300x65.jpg 300w\" sizes=\"(max-width: 600px) 100vw, 600px\" 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