{"id":4684,"date":"2018-06-28T01:00:00","date_gmt":"2018-07-27T06:54:49","guid":{"rendered":"http:\/\/www.05921.net\/index.php\/2018\/07\/27\/%e8%84%82%e8%b4%a8%e7%ba%b3%e7%b1%b3%e7%b2%92%e5%ad%90%ef%bc%9a%e4%bf%83%e8%bf%9b%e5%9f%ba%e5%9b%a0%e7%96%97%e6%b3%95%e4%bb%8e%e6%a6%82%e5%bf%b5%e5%88%b0%e4%b8%b4%e5%ba%8a%e6%95%88%e7%94%a8\/"},"modified":"2018-07-27T14:54:49","modified_gmt":"2018-07-27T06:54:49","slug":"%e8%84%82%e8%b4%a8%e7%ba%b3%e7%b1%b3%e7%b2%92%e5%ad%90%ef%bc%9a%e4%bf%83%e8%bf%9b%e5%9f%ba%e5%9b%a0%e7%96%97%e6%b3%95%e4%bb%8e%e6%a6%82%e5%bf%b5%e5%88%b0%e4%b8%b4%e5%ba%8a%e6%95%88%e7%94%a8","status":"publish","type":"post","link":"https:\/\/www.05921.net\/index.php\/4684\/","title":{"rendered":"\u8102\u8d28\u7eb3\u7c73\u7c92\u5b50\uff1a\u4fc3\u8fdb\u57fa\u56e0\u7597\u6cd5\u4ece\u6982\u5ff5\u5230\u4e34\u5e8a\u6548\u7528"},"content":{"rendered":"
\n

\u3010<\/span><\/strong><\/span>\u975e\u5e38\u611f\u8c22\u4f5c\u8005<\/span><\/strong><\/span>\u201c\u4e09\u4e03\u201d<\/span><\/strong><\/span>\u7684\u6295\u7a3f<\/span><\/strong><\/span>\u3011<\/span><\/strong><\/span><\/p>\n


<\/span><\/strong><\/span><\/p>\n

\u8102\u8d28\u7eb3\u7c73\u7c92\u5b50\uff1a\u4fc3\u8fdb\u57fa\u56e0\u7597\u6cd5\u4ece\u6982\u5ff5\u5230\u4e34\u5e8a\u6548\u7528<\/span><\/strong><\/span><\/p>\n


<\/span><\/strong><\/span><\/p>\n

\u51e0\u4e4e\u4efb\u4f55\u75be\u75c5\u90fd\u53ef\u4ee5\u901a\u8fc7\u6c89\u9ed8\u75c5\u7406\u6027\u57fa\u56e0\u3001\u8868\u8fbe\u6709\u76ca\u86cb\u767d\u6216\u7f16\u8f91\u6709\u7f3a\u9677\u7684\u57fa\u56e0\u6765\u6cbb\u7597\uff0c\u6240\u4ee5\u57fa\u4e8eRNA\u6216DNA\u7684\u57fa\u56e0\u836f\u7269\u5177\u6709\u663e\u8457\u7684\u6cbb\u7597\u6f5c\u529b\u3002\u7136\u800c\uff0c\u57fa\u4e8e\u6838\u9178\u805a\u5408\u7269\u7684\u836f\u7269\u9700\u8981\u590d\u6742\u7684\u4f20\u9012\u7cfb\u7edf\u624d\u53ef\u4ee5\u5c06\u8fd9\u4e9b\u5927\u5206\u5b50\u4f20\u9012\u5230\u9776\u7ec6\u80de\u7684\u5185\u90e8\u3002
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<\/p>\n

\u6240\u4ee5\u6b64\u7c7b\u836f\u7269\u4e34\u5e8a\u5e94\u7528\u7684\u6700\u5927\u969c\u788d\u662f\u5728\u4f53\u5185\u5982\u4f55\u6709\u6548\u5730\u5c06\u57fa\u56e0\u9012\u9001\u5230\u9776\u7ec4\u7ec7\u7ec6\u80de\u5185\u5373\u5408\u9002\u7684\u836f\u7269\u9012\u9001\u7cfb\u7edf\u662f\u4e34\u5e8a\u8bd5\u9a8c\u53d6\u5f97\u6210\u529f\u7684\u6700\u91cd\u8981\u56e0\u7d20\u4e4b\u4e00\u3002<\/span><\/p>\n


<\/span><\/p>\n

\u5728\u514b\u670d\u57fa\u56e0\u4f20\u9012\u969c\u788d\u4e2d<\/span>AlnylamPharmaceuticals\u7684\u7ed9\u51fa\u7684\u8102\u8d28\u7eb3\u7c73\u7c92<\/span>(LNP)\u65b9\u6848\u4e2d\u4e00\u9879\u5173\u952e\u6280\u672f\u5c31\u662f\u5728<\/span>LNP-siRNA\u7cfb\u7edf\u4e2d\u63ba\u5165\u4e86\u4e00\u79cd\u7ecf\u8fc7\u4f18\u5316\u7684\u53ef\u7535\u79bb\u9633\u79bb\u5b50\u8102\u8d28\uff08<\/span>DLIN-MC3-DMA\u6216<\/span>MC3\uff09\u3002\u5728<\/span>LNP-siRNA\u7cfb\u7edf\u4e2d\u63ba\u5165<\/span>MC3\u53ef\u5e26\u6765\u9ad8\u6548\u7684\u57fa\u56e0\u6c89\u9ed8\u6548\u679c\uff0c\u5728\u5c0f\u9f20\u6a21\u578b\u4e2d\uff0c\u5728\u4f4e\u5242\u91cf\u6c34\u5e73\uff08<\/span>5ug siRNA\/\u5c0f\u9f20<\/span> kg\uff09\u4e0b\u53ef\u6709\u6548\u5730\u6c89\u9ed8\u5c0f\u9f20\u809d\u810f\u4e2d\u7684\u57fa\u56e0\u3002<\/span>2017\u5e74<\/span>9\u6708<\/span>AlnylamPharmaceuticals\u7684<\/span>Patisiran\uff08\u4e00\u79cd\u8f7d<\/span>siRNA\u7684<\/span>LNP\u7684\u5236\u5242\uff0c\u7528\u4e8e\u6cbb\u7597\u9057\u4f20\u6027\u80f8\u817a\u80bd\u4ecb\u5bfc\u7684\u6dc0\u7c89\u6837\u53d8\uff09\u901a\u8fc7\u4e86\u4e34\u5e8a\u4e09\u671f\u8bd5\u9a8c\uff0c\u9884\u8ba1\u5c06\u4e8e<\/span>2018\u5e74\u83b7\u5f97<\/span>FDA\u7684\u4e0a\u5e02\u6279\u51c6\u3002\u8fd9\u4e00\u6210\u5c31\u5728\u5f88\u5927\u7a0b\u5ea6\u4e0a\u5f52\u529f\u4e8e\u79bb\u5b50\u5316\u9633\u79bb\u5b50\u8102\u8d28\u7684\u53d1\u5c55\u3002<\/span><\/span><\/p>\n


<\/span><\/p>\n

\u9664\u4e86<\/span>Patisiran\uff0c\u76ee\u524d\u8fd8\u6709<\/span>10\u79cd<\/span>LNP\u9012\u9001\u5c0f\u5206\u5b50\u836f\u7269\u83b7\u5f97\u4e86\u76d1\u7ba1\u6279\u51c6\u3002\u672c\u6587\u5c06\u56de\u987e\u4e86<\/span>LNP\u4f20\u9012\u7cfb\u7edf\u7684\u7814\u7a76\u8fdb\u5c55\uff0c\u4ecb\u7ecd\u4e86<\/span>LNP\u6f5c\u5728\u7684\u5e94\u7528\uff0c\u5305\u62ec\u809d\u4ee5\u5916\u7684\u7ec4\u7ec7\u57fa\u56e0\u6c89\u9ed8\u548c\u57fa\u4e8e<\/span>mRNA\u6216<\/span>CRISPR\u7684\u6cbb\u7597\u65b9\u6cd5\u3002<\/span><\/span><\/p>\n


<\/span><\/p>\n

1 \u57fa\u4e8e\u6838\u9178\u805a\u5408\u7269\u7684\u57fa\u56e0\u6cbb\u7597\u7684\u969c\u788d<\/span><\/strong><\/span><\/h1>\n


<\/span><\/p>\n

\u5728\u4e0a\u4e16\u7eaa<\/span>90\u5e74\u4ee3\uff0c\u57fa\u56e0\u6cbb\u7597\u65e9\u671f\u7814\u7a76\u65b9\u5411\u4fa7\u91cd\u4e8e\u901a\u8fc7\u4f20\u9012<\/span>DNA\u6765\u8bf1\u5bfc\u76ee\u6807\u7ec6\u80de\u8868\u8fbe\u7279\u5b9a\u7684\u57fa\u56e0\u3002\u4f46<\/span>pDNA\u5728\u5c0f\u9f20\u5168\u8840<\/span>(\u4f53\u5916<\/span>)\u4e2d\u7684\u534a\u8870\u671f\u4ec5\u4e3a<\/span>10 min\uff0c\u9759\u8109\u6ce8\u5c04\u540e\u5728\u4f53\u5185\u7684\u534a\u8870\u671f\u751a\u81f3\u66f4\u77ed\uff0c\u540c\u65f6\u8fd8\u6709\u5feb\u901f\u7684\u809d\u79ef\u805a\u3002\u6240\u4ee5\u6838\u9178\u6cbb\u7597\u7684\u7b2c\u4e00\u4e2a\u4e3b\u8981\u969c\u788d\u662f\u8840\u6e05\u6838\u9178\u9176\u6d3b\u6027\u4f7f\u5f97<\/span>pDNA\u5728\u8840\u6e05\u4e2d\u5feb\u901f\u7684\u6d88\u9664\u3002\u7b2c\u4e8c\u4e2a\u969c\u788d\u5c31\u662f\u514d\u75ab\u523a\u6fc0\uff0c\u5c3d\u7ba1\u7ecf\u8fc7\u5316\u5b66\u4fee\u9970\u7684\u6838\u9178\u53ef\u4ee5\u90e8\u5206\u89c4\u907f\u8fd9\u79cd\u514d\u75ab\u53cd\u5e94\uff0c\u4f46\u4ece\u751f\u7269\u6765\u6e90\u7eaf\u5316\u7684<\/span>pDNA\uff0c\u5e76\u975e\u5408\u6210\u800c\u6765\uff0c\u4e0d\u9002\u5408\u8fd9\u79cd\u4fee\u9970\u3002\u5e76\u4e14\u5728\u751f\u7269\u7eaf\u5316\u8fc7\u7a0b\u4e2d\u4e5f\u6613\u53d7\u5230\u539f\u6750\u6599\u4e2d\u70ed\u539f\uff08\u5185\u6bd2\u7d20\uff09\u7684\u5f71\u54cd\u3002<\/span><\/span><\/p>\n


<\/span><\/span><\/p>\n

\u4f46\u662f\uff0c\u5373\u4f7f\u88ab\u7ecf\u8fc7\u5927\u91cf\u4fee\u9970\u7684\u6838\u9178\u8de8\u8fc7\u4e86\u524d\u4e24\u4e2a\u969c\u788d\uff0c\u5b83\u4eec\u4ecd\u7136\u53d7\u5230\u7b2c\u4e09\u79cd\u969c\u788d\u7684\u5f71\u54cd\u2014\u2014\u80be\u8fc7\u6ee4\uff08\u5c0f\u4e8e<\/span>6nm\u7684\u9897\u7c92\u7684\u9ad8\u6548\u8fc7\u6ee4\uff09\u3002\u5bf9\u5be1\u6838\u82f7\u9178\u836f\u52a8\u5b66\u7684\u7814\u7a76\u8868\u660e\uff0c<\/span>50%\u4ee5\u4e0a\u7684\u836f\u7269\u5728\u5c3f\u6db2\u4e2d\u6392\u6cc4\u3002\u8fd9\u4e9b\u7814\u7a76\u8868\u660e\u672a\u4fee\u9970\u7684\u6838\u9178\u805a\u5408\u7269\u4f5c\u4e3a\u6cbb\u7597\u5242\uff0c\u7531\u4e8e\u5176\u751f\u7269\u5229\u7528\u5ea6\u5dee\u800c\u5e94\u7528\u53d7\u5230\u9650\u5236\u3002<\/span><\/span><\/p>\n


<\/span><\/p>\n

\u4e3a\u4e86\u514b\u670d\u8fd9\u4e9b\u969c\u788d\uff0c\u5df2\u7ecf\u6709\u5173\u4e8e\u8bb8\u591a\u9012\u9001\u7cfb\u7edf\u7684\u63a2\u7d22\u3002\u5728\u672c\u4e2d\uff0c\u6211\u4eec\u4e3b\u8981\u4ecb\u7ecd\u8102\u8d28\uff0c\u6700\u65e9\u662f<\/span>Felgner\u7b49\u4eba\u5229\u7528\u6b63\u7535\u8377\u8102\u8d28<\/span> DOTMA\u5728\u4f53\u5916\u7814\u7a76\u53d1\u73b0\uff0c\u6b63\u7535\u8377\u8102\u8d28\u8f6c\u67d3\u6bd4\u78f7\u9178\u9499\u548c\u7cd6\u82f7\u4ecb\u5bfc\u7684\u8f6c\u67d3\u6548\u529b\u5f3a\u4e86<\/span>5\u81f3<\/span>100\u500d\u3002\u8fd9\u9879\u7814\u7a76\u5f00\u59cb\u4e86\u57fa\u4e8e\u8102\u8d28\u7684\u8f7d\u4f53\u9012\u9001\u6838\u9178\u7684\u7814\u7a76\u3002<\/span><\/span><\/p>\n


<\/span><\/p>\n

2  \u7528\u4e8e\u9012\u9001\u6838\u9178\u7684<\/span>LNP\u7684\u8bbe\u8ba1<\/span><\/span><\/strong><\/span><\/h1>\n


<\/span><\/p>\n

LNP\u8f7d\u8fd0\u5c0f\u5206\u5b50\u836f\u7269\u7684\u5236\u5242\u6280\u672f\u5df2\u7ecf\u76f8\u5bf9\u6210\u719f\uff0c\u5b83\u5177\u6709\u9002\u5b9c\u7684\u7c92\u5f84\uff08<\/span>100nm\u76f4\u5f84\u6216\u66f4\u5c0f\uff09\uff0c\u9ad8\u5c01\u88c5\u6548\u7387\uff0c\u5236\u5907\u5de5\u827a\u7a33\u5b9a\u3001\u8868\u9762\u7535\u8377\u4f4e\u7684\u7279\u70b9\uff08\u4f4e\u8868\u9762\u7535\u8377\u53ef\u4ee5\u51cf\u5c11\u4e0e\u8840\u6e05\u86cb\u767d\u7684\u76f8\u4e92\u4f5c\u7528\uff09\u3002\u901a\u8fc7\u4e0d\u540c\u7684\u8f7d\u836f\u7b56\u7565\u548c\u5236\u5907\u6280\u672f\uff0c<\/span>LNP\u8f7d\u836f\u7cfb\u7edf\u53ef\u4ee5\u5b9e\u73b0\u6838\u9178\u805a\u5408\u7269\u7684\u6709\u6548\u805a\u96c6\uff08<\/span>> 80\uff05\uff09\u548c\u9012\u9001\u3002\u9633\u79bb\u5b50\u8102\u8d28\u53ef\u4ee5\u5b9e\u73b0\u8d1f\u7535\u8377\u7684\u805a\u5408\u7269\u7684\u5305\u5c01\uff0c\u800c\u8fd9\u7c7b\u9633\u79bb\u5b50\u8102\u8d28\u7814\u53d1\uff0c\u5982\u4e0b\u6240\u8ff0\u7ecf\u5386\u4e86\u76f8\u5f53\u957f\u7684\u8fc7\u7a0b\u3002<\/span><\/span><\/p>\n


<\/span><\/p>\n

2.1 \u9633\u79bb\u5b50\u8102\u8d28\u548c\u201c<\/span>lipoplexes\u201d<\/span><\/span><\/strong><\/h2>\n


<\/span><\/p>\n

\u65e9\u671f\u5f00\u53d1<\/span>LNP\u7cfb\u7edf\u7684\u4e3b\u8981\u52aa\u529b\u65b9\u5411\u662f\u5229\u7528\u4e2d\u6027<\/span>(\u4e24\u6027\u79bb\u5b50<\/span>)\u8102\u7c7b\u7684\u88ab\u52a8\u5f0f\u5305\u5c01\u6cd5\uff0c\u8fd9\u79cd\u65b9\u6cd5\u5229\u7528\u9759\u7535\u7279\u6027\u6765\u5b9e\u73b0\u5305\u5c01\u3002\u4f46\u6709\u5305\u5c01\u6548\u7387\u8f83\u5dee\uff08<\/span><40\uff05\uff09\u3001\u8f6c\u67d3\u6548\u529b\u6709\u9650\u7684\u7f3a\u70b9<\/span><\/span><\/p>\n

\u201c<\/span>lipoplexes\u201d\u662f\u57fa\u4e8e<\/span>DOTMA\u7684\u7814\u53d1\u7684\u590d\u5408\u7269\uff0c\u5c06<\/span>DOTMA\u4e0e\u4e00\u79cd\u201c\u8f85\u52a9\u6027\u8102\u201d\u2014\u2014\u4e8c\u6cb9\u57fa\u78f7\u8102\u9170\u4e59\u9187\u80fa<\/span>(DOPE)\u7ed3\u5408\u5728\u4e00\u8d77\uff0c\u5e76\u4e0e<\/span>DNA\u5728\u6eb6\u6db2\u4e2d\u7ed3\u5408\uff0c\u4ece\u800c\u83b7\u5f97\u66f4\u9ad8\u7684\u5305\u5c01\u7387\u3001\u66f4\u9ad8\u6548\u7684\u8f6c\u67d3\u80fd\u529b\u3002\u4f46\u201c<\/span>Lipoplexes\u201d\u7c92\u5f84\u8303\u56f4\u4ece\u4e9a\u5fae\u7c73\u5c3a\u5ea6\u5230\u51e0\u5fae\u7c73\u4e0d\u7b49\uff0c\u5b58\u5728\u70ed\u529b\u5b66\u4e0d\u7a33\u5b9a\u7684\u95ee\u9898\u3002<\/span>Lipoplexes\u7c7b\u7684\u4ee3\u8868<\/span> Lipofectamine\u00ae\u8bd5\u5242\uff0c\u5177\u6709\u8f83\u5f3a\u7684\u4f53\u5916\u8f6c\u67d3\u6548\u529b\u3002\u8fd9\u4e9b\u7b2c\u4e00\u4ee3<\/span>Lipoplexes\uff0c\u7c92\u5f84\u8f83\u5927\u548c\u6b63\u7535\u8377\u6027<\/span>(\u7531\u9633\u79bb\u5b50\u8102\u8d28\u4f20\u9012\uff0c\u5bfc\u81f4\u8840\u6d46\u8fc5\u901f\u6e05\u9664<\/span>)\uff0c\u8fd8\u6709\u6eb6\u8840\u3001\u514d\u75ab\u539f\u6027\u3002\u548c\u5176\u4ed6\u6bd2\u6027\u7684\u7f3a\u70b9\u9650\u5236\u4e86\u5b83\u5728\u6d3b\u4f53\u5b9e\u9a8c\u7684\u7814\u7a76\u3002<\/span><\/span><\/p>\n


<\/span><\/strong><\/p>\n

2.2  \u9633\u79bb\u5b50\u8102\u8d28\u548c<\/span>LNPs<\/span><\/strong><\/h2>\n


<\/span><\/p>\n

\u7b2c\u4e00\u4ee3\u8f7d\u8fd0\u9057\u4f20\u836f\u7269<\/span>(pDNA) \u7684<\/span>LNP\u5236\u5907\u65b9\u6848\u662f\u91c7\u7528\u9633\u79bb\u5b50\u8102\u8d28\u901a\u8fc7\u6d17\u6da4<\/span>–\u900f\u6790\u7684\u6280\u672f\u5236\u5907\u3002\u8be5\u65b9\u6cd5\u662f\u5c06<\/span>pDNA\u4e0e\u9633\u79bb\u5b50\u8102\u8d28\uff08<\/span>DODAC\uff09\u540c<\/span>OGP\u7b49\u6d17\u6da4\u5242\u6df7\u5408\uff0c\u7136\u540e\u5728<\/span>OGP\u6eb6\u6db2\u4e2d\u52a0\u5165\u542b\u5375\u78f7\u8102\u548c<\/span>PEG-\u8102\u7684\u6eb6\u6db2\u3002\u6700\u540e\u7684\u6df7\u5408\u7269\u88ab\u900f\u6790<\/span>36-48\u5c0f\u65f6\uff0c\u53bb\u9664\u6d17\u6da4\u5242\u5e76\u5f62\u6210\u7eb3\u7c73\u9897\u7c92\u3002\u5f53\u9633\u79bb\u5b50\u8102\u8d28\u542b\u91cf\u4e3a<\/span>6~8 mol%\u65f6\uff0c\u5305\u5c01\u7387\u4e3a<\/span>30%\uff0c\u8fdb\u4e00\u6b65\u7528<\/span>DOPE\u4ee3\u66ff\u5375\u78f7\u8102\u65f6\uff0c\u5305\u5c01\u7387\u53ef\u4ee5\u8fbe\u5230<\/span>70%\u3002\u8fd9\u4e9b\u9897\u7c92\u88ab\u79f0\u4e3a<\/span>SPLP (stabilizedplasmid-lipid-particles)\uff0c\u5728\u4f4e\u6e29\u900f\u5c04\u7535\u955c\u4e0b\u5448\u5355\u7247\u72b6\u7ed3\u6784\uff0c\u7c92\u5f84\u5206\u5e03\u5728<\/span>70 nm\u5de6\u53f3\u3002<\/span><\/span><\/p>\n


<\/span><\/p>\n

SPLP\u5177\u6709\u4f53\u5185\u957f\u5faa\u73af\u7279\u6027\uff0c\u5728\u5c0f\u9f20\u4e2d<\/span>t1\/2<\/sub>\u4e3a<\/span> 7\u5c0f\u65f6\uff0c\u800c\u88f8\u9732\u7684<\/span>t1\/2 <\/sub>\u5c0f\u4e8e<\/span>DNA 10\u5206\u949f\u3002\u8fd9\u4f7f\u5f97<\/span>2.5\uff05\u7684\u6ce8\u5c04\u5242\u91cf\u5728<\/span>24\u5c0f\u65f6\u5185\u5728\u8fdc\u7aef\u80bf\u7624\u5904\u79ef\u7d2f\uff0c\u540c\u65f6\u5728\u809d\u810f\u548c\u813e\u810f\u4e2d\u6c34\u5e73\u975e\u5e38\u4f4e\u3002\u91cd\u8981\u7684\u662f\uff0c\u4e0e<\/span>Lipoplexes\u76f8\u6bd4\uff0c<\/span>SPLP\u7684\u809d\u6bd2\u6027\u660e\u663e\u964d\u4f4e\uff0c\u5728<\/span>30 mg DNA\u7684\u5242\u91cf\u4e0b<\/span>Lipoplexes\u53ef\u4f7f\u8840\u6e05\u4e2d\u7684\u4e19\u6c28\u9178\u8f6c\u6c28\u9176<\/span>(ALT)\u548c\u5929\u51ac\u6c28\u9178\u8f6c\u6c28\u9176<\/span>(AST)\u7684\u6c34\u5e73\u589e\u52a0<\/span>100\u500d\uff0c\u800c<\/span>175 mg DNA\u7684<\/span>SPLP\u5728\u8840\u6e05\u4e2d\u68c0\u6d4b\u5230<\/span>ALT\u548c<\/span>AST\u7684\u5904\u5728\u57fa\u7ebf\u6c34\u5e73\u3002\u7136\u800c\uff0c\u7531\u4e8e\u5305\u5c01\u7387\u4f4e\u3001\u6548\u529b\u6709\u9650\u4ee5\u53ca\u6d17\u6da4\u5242\u900f\u6790\u5236\u9020\u6280\u672f\u662f\u5355\u4e00\u4e14\u4e0d\u53ef\u6269\u5c55\u7684\u539f\u56e0\uff0c\u963b\u788d\u4e86<\/span>SPLP\u65b9\u6cd5\u7684\u8fdb\u4e00\u6b65\u524d\u8fdb\u3002<\/span><\/span><\/p>\n


<\/span><\/p>\n

2.3 \u53ef\u79bb\u5b50\u5316\u7684\u9633\u79bb\u5b50\u8102\u8d28\u548c\u4e59\u9187\u8f7d\u8377<\/span><\/span><\/strong><\/h2>\n


<\/span><\/p>\n

\u6d17\u6da4<\/span>–\u900f\u6790\u5236\u5907\u8fc7\u7a0b\u867d\u7136\u53ef\u4ee5\u751f\u4ea7\u5747\u5300\u7684<\/span>LNP\uff0c\u4f46\u5236\u5907\u6548\u7387\u4f4e\u4e0b\u3002\u56e0\u6b64\uff0c\u4e59\u9187\u8377\u8f7d\u5de5\u827a\u53ef\u4ee5\u4e0e\u53ef\u7535\u79bb\u7684\u9633\u79bb\u5b50\u8102\u8d28\u7ed3\u5408\u4f7f\u7528\u3002\u6700\u521d\u7684\u65b9\u6cd5\u662f\u7528\u4e59\u9187\u6eb6\u89e3\u8102\u8d28\uff0c\u5e76\u5c06\u8be5\u6eb6\u6db2\u52a0\u5165\u5230<\/span>pH4\u7f13\u51b2\u6db2\u4e2d\u7684\u53cd\u4e49\u5be1\u6838\u82f7\u9178<\/span>(Aso)\u6c34\u6eb6\u6db2\u4e2d\u3002\u7136\u540e\u5c06\u4ea7\u751f\u7684\u7c92\u5b50\u6324\u51fa\uff0c\u5f97\u5230\u5747\u76f8\u7684\u7c92\u5b50\u7fa4\u4e3a<\/span>100 nm\u7684<\/span>LNP\uff0c\u7136\u540e\u900f\u6790\u53bb\u9664\u6eb6\u5242\uff0c\u4e2d\u548c<\/span>pH\u503c\u3002\u8be5\u5de5\u827a\u5305\u5c01\u7387\u53ef\u4ee5\u8fbe\u5230<\/span>80%\u3002\u5728\u4e0b\u4e00\u4ee3\u6280\u672f\u4e2d\uff0c\u8102\u8d28\u4f53\u6700\u521d\u662f\u901a\u8fc7\u6324\u538b\u5f62\u6210\u7684\uff0c\u7136\u540e\u5728\u9178\u6027<\/span>pH\u6761\u4ef6\u4e0b\uff0c<\/span>40%(v\/v)\u4e59\u9187\u6d53\u5ea6\u6ce8\u5165<\/span>ASO\u3002\u6240\u5f97\u7c92\u5b50\u5bf9<\/span>ASO\u548c<\/span>pDNA\u7cfb\u7edf\u7684\u5305\u5c01\u7387\u5206\u522b\u9ad8\u8fbe<\/span>90%\u548c<\/span>70%\u3002<\/span><\/span><\/p>\n


<\/span><\/p>\n

\u6700\u65b0\u4e00\u4ee3\u4e59\u9187\u8377\u8f7d\u662f\u4f7f\u7528<\/span>Batzri\u548c<\/span>Korn\u4e59\u9187\u6ce8\u5c04\u6cd5\u4e4b\u540e\u4f7f\u7528\u81ea\u53d1\u5f62\u6210\u56ca\u6ce1\u7684\u8fc7\u7a0b\u3002\u5728\u8fd9\u4e2a\u8fc7\u7a0b\u4e2d\uff0c\u8102\u8d28\u4ee5\u9002\u5f53\u7684\u6bd4\u4f8b\u6eb6\u89e3\u5728\u4e59\u9187\u4e2d\uff0c\u800c<\/span>pDNA\u6eb6\u89e3\u5728\u9178\u6027\u7f13\u51b2\u6db2\u4e2d\uff0c\u6eb6\u6db2\u5feb\u901f\u6df7\u5408\u5305\u5c01\u7387\u53ef\u4ee5\u8fbe\u5230<\/span>60%\uff0c\u7136\u540e\u7acb\u5373\u5c06\u5f97\u5230\u7684\u7eb3\u7c73\u7c92\u5b50\u8fdb\u4e00\u6b65\u7528\u4e59\u9187\u7a00\u91ca\u540e\u5305\u5c01\u7387\u8fbe\u5230\u4e86<\/span>80~90%\uff0c\u5b9e\u73b0\u6709\u6548\u7684\u5c01\u88c5\u3002<\/span><\/span><\/p>\n


<\/span><\/p>\n

3 \u53ef\u79bb\u5b50\u5316\u9633\u79bb\u5b50\u8102\u8d28<\/span>LNPs\u7528\u4e8e<\/span>siRNA\u7684\u4f20\u9012<\/span><\/span><\/strong><\/span><\/h1>\n


<\/span><\/p>\n

\u4e59\u9187\u8377\u8f7d\u6280\u672f\u4e0e<\/span>DODAP\u7b49\u53ef\u79bb\u5b50\u5316\u9633\u79bb\u5b50\u8102\u8d28\u8054\u5408\u5236\u5907\u7684<\/span>ASO-LNP\u5177\u6709\u8f83\u597d\u7684\u836f\u52a8\u5b66\u7279\u5f81\uff0c\u4f46\u5bf9\u63d0\u9ad8<\/span>ASO\u57fa\u56e0\u6c89\u9ed8\u80fd\u529b\u6709\u9650\uff0c\u4f46\u540e\u6765\u5374\u53d1\u73b0\u9012\u9001<\/span>siRNA\u5230\u809d\u810f\u90e8\u4f4d\u4f1a\u6536\u5230\u66f4\u597d\u7684\u57fa\u56e0\u6c89\u9ed8\u6548\u679c\u3002<\/span><\/span><\/p>\n


<\/span><\/p>\n

3.1 \u53ef\u79bb\u5b50\u5316\u9633\u79bb\u5b50\u8102\u8d28\u7684\u8bbe\u8ba1\u53ca\u4e34\u5e8a\u5e94\u7528<\/span><\/span><\/strong><\/h2>\n


<\/span><\/p>\n

\u91c7\u7528\u53ef\u79bb\u5b50\u5316\u9633\u79bb\u5b50\u8102\u8d28\u7684\u6700\u521d\u539f\u56e0\u662f\u4e3a\u4e86\u5b9e\u73b0\u5728\u4f4e<\/span>pH\u6761\u4ef6\u4e0b\u5bf9\u5e26\u8d1f\u7535\u805a\u5408\u7269\u7684\u6709\u6548\u5305\u5c01\uff0c\u5e76\u4e14\u5728<\/span>pH7.4\u65f6\u4e5f\u663e\u793a\u51fa\u76f8\u5bf9\u65e0\u7535\u8377\u7684\u8868\u9762\u3002\u7136\u800c\uff0c\u7ecf\u9759\u8109\u7ed9\u836f\u7684<\/span>LNP-siRNA\u7cfb\u7edf\u5bf9\u809d\u7ec6\u80de\u57fa\u56e0\u6c89\u9ed8\u7814\u7a76\u53d1\u73b0\u9009\u7528\u7684\u79bb\u5b50\u5316\u9633\u79bb\u5b50\u8102\u8d28\u81f3\u5173\u91cd\u8981\u3002\u5728\u8fdb\u4e00\u6b65\u7684\u8fdb\u884c\u5168\u9762\u7684\u8102\u8d28\u7b5b\u9009\u8fc7\u7a0b\u4e2d\uff0c\u4e00\u4e2a\u91cd\u8981\u7684\u539f\u5219\u5c31\u662f\uff0c\u53ef\u79bb\u5b50\u5316\u9633\u79bb\u5b50\u8102\u8d28\u5fc5\u987b\u6709\u5408\u9002\u7684<\/span>pKa\uff0c\u53ea\u6709\u8db3\u591f\u9ad8\u7684<\/span>pKa\u7684<\/span>LNP\u5728\u5185\u6db5\u4f53\u9178\u6027<\/span>pH\u503c\u4e0b\uff0c\u9633\u79bb\u5b50\u8102\u8d28\u5c31\u80fd\u4e0e\u5185\u6e90\u6027\u5185\u8d28\u9634\u79bb\u5b50\u8102\u8d28\u7ed3\u5408\uff0c\u5f62\u6210\u4fc3\u8fdb\u819c\u6eb6\u89e3\u7684\u975e\u53cc\u5c42\u7ed3\u6784\uff0c\u4ece\u800c\u4ece\u7ec6\u80de\u5185\u7684\u91ca\u653e\uff0c\u4f46\u8fc7\u9ad8\u7684<\/span>pKa\u4f7f\u5f97<\/span>LNP\u5728\u751f\u7406<\/span>pH\u503c\u4e0b\u5177\u6709\u9ad8\u7684\u8868\u9762\u6b63\u7535\u8377\uff0c\u53ef\u4ee5\u5438\u9644\u8840\u6e05\u86cb\u767d\uff0c\u5e76\u8fc5\u901f\u4ece\u5faa\u73af\u4e2d\u6e05\u9664\u3002<\/span><\/span><\/p>\n


<\/span><\/p>\n

\u5728\u5c0f\u9f20\u56e0\u5b50<\/span>F VII(FVII)\u809d\u57fa\u56e0\u6c89\u9ed8\u6a21\u578b\uff0c\u5bf9\u542b\u6709\u591a\u79cd\u53ef\u7535\u79bb\u9633\u79bb\u5b50\u8102\u8d28\u7684<\/span>LNPs\u8fdb\u884c\u8bc4\u4ef7\uff0c\u786e\u5b9a\u5b9e\u73b0<\/span>50%\u57fa\u56e0\u6c89\u9ed8\uff08<\/span>ED50\uff09\u7684\u6709\u6548\u5242\u91cf\u3002<\/span>DLIN-KC2-DMA\uff08<\/span>KC2\uff09\u4f5c\u4e3a\u53ef\u79bb\u5b50\u5316\u7684\u9633\u79bb\u5b50\u8102\u8d28\uff0c\u4e0e<\/span>DLIDEMA\u76f8\u6bd4\u5177\u6709\u6539\u5584\u7684\u6d3b\u6027\uff0c\u800c<\/span>MC3-LNP\u7684<\/span>ED 50\u8fdb\u4e00\u6b65\u964d\u4f4e\u4e14\u6bd2\u6027\u65e0\u589e\u52a0\uff0c\u5177\u5907\u4e86\u4e34\u5e8a\u5e94\u7528\u7684\u53ef\u80fd\u3002<\/span><\/span><\/p>\n


<\/span><\/p>\n

\u6240\u4ee5<\/span>Alnylam Pharmaceuticals\u7684\u91c7\u7528<\/span>MC3\u6784\u5efa<\/span>LNP-siRNA\u2014\u2014<\/span>Patisiran\uff0c\u7528\u4ee5\u9759\u9ed8\u7531<\/span>TTR\u57fa\u56e0\u7a81\u53d8\u4ee5\u6cbb\u7597\u9057\u4f20\u6027\u8fd0\u7532\u72b6\u817a\u7d20\u86cb\u767d<\/span>(TTR)\u4ecb\u5bfc\u6dc0\u7c89\u6837\u53d8\u5f15\u8d77\u7684\u81f4\u547d\u75be\u75c5\u3002\u7814\u7a76\u53d1\u73b0\u8fd9\u4e00\u7a81\u53d8\u5bf9\u542b<\/span>MC3\u7684<\/span>LNP-siRNA\u5f15\u8d77\u7684\u57fa\u56e0\u6c89\u9ed8\u6781\u4e3a\u654f\u611f\u3002\u5728\u4e00\u671f\u4e34\u5e8a\u4e2d\u5728<\/span>0.5 mg siRNA\/kg\u65f6\u4eba\u4f53\u8010\u53d7\u6781\u597d\uff0c\u800c\u4e8c\u671f\u4e34\u5e8a\u5b9e\u9a8c\u4e2d<\/span>0.3 mg siRNA\/kg\u5c31\u53ef\u4ee5\u6536\u5230\u5f88\u597d\u7684\u57fa\u56e0\u6c89\u9ed8\u6548\u679c\uff0c\u5728<\/span>2017\u5e74<\/span>9\u6708\u4e09\u671f\u4e34\u5e8a\u8bd5\u9a8c\u4e5f\u53d6\u5f97\u4e86\u6781\u4f73\u7684\u6210\u679c\uff0c\u8fbe\u5230\u4e86\u4e3b\u8981\u7ec8\u70b9\u548c\u6240\u6709\u6b21\u8981\u7ec8\u70b9\uff0c\u968f\u540e\u5411<\/span>FDA\u63d0\u51fa\u4e0a\u5e02\u7533\u8bf7\uff0c\u81f3\u6b64\u7b2c\u4e00\u6b3e<\/span>RNAi\u7c7b\u836f\u7269\u6709\u671b\u83b7\u5f97\u4e0a\u5e02\u6279\u51c6\u3002<\/span><\/span><\/p>\n


<\/span><\/p>\n

4 \u672a\u6765\u53d1\u5c55<\/span><\/span><\/strong><\/span><\/h1>\n


<\/span><\/p>\n

LNP-siRNA\u7cfb\u7edf\u5728\u809d\u7ec6\u80de\u4e2d\u6c89\u9ed8<\/span>TTR\u57fa\u56e0\u7684\u6210\u529f\u6253\u5f00\u4e86\u4e00\u6247\u6c89\u9ed8\u809d\u7ec6\u80de\u4e2d\u7684\u57fa\u56e0\u7684\u5927\u95e8\uff0c\u4f8b\u5982\u7528\u4e8e\u964d\u80c6\u56fa\u9187\u6cbb\u7597\u7684<\/span>PCSK9\u57fa\u56e0\u3002\uff08<\/span>Kexin\u6837\u524d\u8f6c\u5316\u9176\u67af\u8349\u6746\u83cc\u86cb\u767d\u9176\u5bb6\u65cf\u7684\u7b2c<\/span>9\u4e2a\u6210\u5458\uff09\u3002<\/span><\/span><\/p>\n


<\/span><\/p>\n

\u4f46\u672a\u6765\u5176\u4ed6\u7684\u5e94\u7528\u4e0d\u4ec5\u4ec5\u5c40\u9650\u4e8e\u809d\u810f\u7ec6\u80de\uff0c\u4f7f\u7528<\/span>LNP\u7cfb\u7edf\u53ef\u4ee5\u6c89\u9ed8\u809d\u810f\u4ee5\u5916\u7684\u7ec4\u7ec7\u4e2d\u7684\u57fa\u56e0\uff0c\u5982\u6c89\u9ed8\u81f4\u764c\u57fa\u56e0\uff0c\u6cbb\u7597\u8bf8\u5982\u764c\u75c7\u7684\u75be\u75c5\u3002\u53e6\u4e00\u65b9\u9762\uff0c<\/span>LNP\u6280\u672f\u7684\u5ef6\u4f38\u5230\u9012\u9001<\/span>mRNA\u4e3a\u6cbb\u7597\u6027\u86cb\u767d\u8d28\u7684\u8868\u8fbe\u63d0\u4f9b\u53ef\u80fd\uff0c\u53ef\u4ee5\u6cbb\u7597\u5404\u79cd\u9700\u8981\u86cb\u767d\u8d28\u66ff\u4ee3\u7684\u75be\u75c5\u3002\u6700\u540e\uff0c\u6269\u5c55<\/span>CRSPR-CAS\u5728\u4f53\u5185\u8fdb\u884c\u57fa\u56e0\u7f16\u8f91\u7684\u53ef\u4ee5\u6cbb\u7597\u8bb8\u591a\u9057\u4f20\u75c5\u3002\u5176\u4e2d\u4e00\u4e9b\u76ee\u524d\u6b63\u5728\u4e34\u5e8a\u8bd5\u9a8c\u4e2d\u8fdb\u884c\u8bc4\u4f30\u3002<\/span><\/span><\/p>\n


<\/span><\/p>\n

4.1 \u809d\u5916\u9776\u533a<\/span>LNP-siRNA\u7684\u8bbe\u8ba1<\/span><\/span><\/strong><\/h2>\n


<\/span><\/p>\n

\u9012\u9001\u5c0f\u5206\u5b50\u6cbb\u7597\u836f\u7269\u7684\u8102\u8d28\u4f53\u7cfb\u7edf\u901a\u5e38\u4f7f\u7528\u805a\u4e59\u4e8c\u9187\u8102\u8d28\u4fee\u9970\u6765\u589e\u52a0\u5faa\u73af\u65f6\u95f4\uff0c\u4ece\u800c\u6539\u5584\u809d\u5916\u9776\u90e8\u4f4d\u7684\u8f6c\u8fd0\u80fd\u529b\u3002\u7136\u800c\uff0c\u5c06\u805a\u4e59\u4e8c\u9187\u8102\u8d28<\/span>(\u5982<\/span>PEG-DSG)\u63ba\u5165<\/span>LNP-siRNA\u7cfb\u7edf\u5c3d\u7ba1\u53ef\u4ee5\u5b9e\u73b0\u4f53\u5185\u957f\u5faa\u73af\uff0c\u5b9e\u73b0\u6301\u4e45\u6027\u809d\u5916\u5206\u5e03\uff0c\u4f46\u5927\u5927\u964d\u4f4e\u4e86\u8f6c\u67d3\u80fd\u529b\uff0c\u8fd9\u5c31\u662f\u8fd8\u6709\u5f85\u89e3\u51b3\u7684<\/span> \u2018PEG\u56f0\u5883<\/span>\u2019\u3002<\/span><\/span><\/p>\n


<\/span><\/p>\n

\u4e00\u9879<\/span>LNP-siRNA(\u542b\u6709<\/span>PEG-DSG 3-5 mol%\uff0c\u7c92\u5f84<\/span>30 nm\uff0c\u534a\u8870\u671f<\/span>10-12 h)\uff0c\u6572\u9664\u524d\u5217\u817a\u764c\u7684\u57fa\u672c\u9a71\u52a8\u56e0\u5b50\u96c4\u6fc0\u7d20\u53d7\u4f53<\/span>(AR)\u7814\u7a76\u4e2d\u53d1\u73b0\u3002\u5b9e\u73b0\u660e\u663e\u57fa\u56e0\u6c89\u9ed8\u6240\u9700\u7684<\/span>LNP-siRNA\u5242\u91cf\u4e3a<\/span>30 mg\/kg\uff0c\u4f46\u662f\u8fbe\u5230\u809d\u7ec6\u80de<\/span>ED 50<\/sub>\u7684<\/span>6000\u500d\u3002\u4e3a\u4e86\u63d0\u9ad8\u6548\u80fd\uff0c\u6211\u4eec\u52a0\u5165\u4e86\u524d\u5217\u817a\u7279\u5f02\u6027\u819c\u6297\u539f\u7684\u9776\u5411\u914d\u4f53\uff0c\u4ece\u800c\u63d0\u9ad8\u4e86\u57fa\u56e0\u6c89\u9ed8\u7684\u80fd\u529b\uff0c\u4f46\u4e0d\u80fd\u8fbe\u5230\u4e34\u5e8a\u6f5c\u529b\u6240\u9700\u7684\u6570\u91cf\u7ea7\u6539\u8fdb\u3002\u8fd8\u4e0d\u503c\u5f97\u4e34\u5e8a\u5f00\u53d1\u3002<\/span><\/span><\/p>\n


<\/span><\/p>\n

\u4e2d\u67a2\u795e\u7ecf\u7cfb\u7edf\u4e2d<\/span>LNP-siRNA\u8f6c\u8fd0\u4e0e\u809d\u7ec6\u80de\u4e2d\u8f6c\u8fd0\u7684\u539f\u7406\u76f8\u540c\uff08<\/span>ApoE\u53d7\u4f53\uff09\uff0c\u7136\u800c\uff0c<\/span>LNP-siRNA\u7cfb\u7edf\u65e0\u6cd5\u7a7f\u900f\u8840\u8111\u5c4f\u969c\uff0c\u9700\u8981\u901a\u8fc7\u8111\u5ba4\u5185\u7ed9\u836f\u5b9e\u73b0\u6ce8\u5c04\u90e8\u4f4d\u5468\u56f4\u7684\u6c89\u9ed8\u3002\u4e00\u9879\u5173\u4e8e<\/span>LNP-siRNA\u4ecb\u5bfc\u7684\u57fa\u56e0\u6572\u9664\u5b9e\u9a8c\u4e2d\uff0c\u5b9e\u73b0\u4e86\u5bf9<\/span>SLC26A11\u7684\u6291\u5236\uff0c\u663e\u8457\u51cf\u8f7b\u4e86\u795e\u7ecf\u5143\u80bf\u80c0\u3002\u8fd9\u4e9b\u7814\u7a76\u8bc1\u5b9e<\/span>LNP-siRNA\u5177\u6709\u9776\u6807\u8bc6\u522b\u7684\u6f5c\u529b\uff0c\u4ee5\u53ca\u901a\u8fc7\u9798\u5185\u3001\u5ba4\u95f4\u6216\u9798\u5185\u9014\u5f84\u76f4\u63a5\u7ed9\u836f\u7684\u6cbb\u7597\u4e25\u91cd\u75be\u75c5\u7684\u5e94\u7528\u6f5c\u529b<\/span><\/span><\/p>\n


<\/span><\/p>\n

4.2 \u7528\u4e8e\u57fa\u56e0\u8868\u8fbe\u548c\u7f16\u8f91\u7684<\/span>LNP\u8bbe\u8ba1<\/span><\/span><\/strong><\/h2>\n


<\/span><\/p>\n

\u968f\u7740\u5c06<\/span>siRNA\u5305\u88f9\u5230<\/span>LNP\u4e2d\u7684\u4e59\u9187\u8377\u8f7d\u6280\u672f\u7684\u53d1\u5c55\uff0c\u8fd9\u79cd\u65b9\u6cd5\u4e5f\u53ef\u4ee5\u7528\u6765\u5c01\u88c5<\/span>mRNA\u3001<\/span>pDNA\u548c\u5176\u4ed6\u5e26\u8d1f\u7535\u8377\u7684\u5927\u5206\u5b50\u3002\u8fd9\u5e26\u6765\u4e86\u57fa\u4e8e<\/span>mRNA\u7684\u7597\u6cd5\u7684\u91cd\u5927\u8fdb\u5c55\u3002<\/span><\/span><\/p>\n

\u76ee\u524d\u5df2\u7ecf\u5f00\u5c55\u4e86\u5927\u91cf\u4f18\u5316\u8f7d\u8fd0<\/span>mRNA\u7684\u53ef\u79bb\u5b50\u5316\u7684\u9633\u79bb\u5b50\u8102\u8d28\u7684\u7684\u7684\u7814\u53d1\uff0c\u5982\u9759\u8109\u6ce8\u5c04\u542b\u6709\u672a\u7ecf\u4fee\u9970\u7684\u3001\u7f16\u7801\u4fc3\u7ea2\u7ec6\u80de\u751f\u6210\u7d20<\/span>(EPO)\u7684\u5e8f\u5217\u5de5\u7a0b<\/span>mRNA-LNP\uff0c\u5728\u732a\u548c\u7334\u4e0a\u5b9e\u9a8c\u90fd\u53ef\u4ee5\u5347\u9ad8<\/span>Epo\u6c34\u5e73\uff0c\u589e\u52a0\u7f51\u7ec7\u7ea2\u7ec6\u80de\u6570\uff0c\u5e76\u63d0\u9ad8\u7ea2\u7ec6\u80de\u538b\u79ef\u3002\u8fd9\u8bf4\u660e\u4e86\u5229\u7528\u809d\u810f\u4f5c\u4e3a\u751f\u7269\u53cd\u5e94\u5668\u8868\u8fbe\u6cbb\u7597\u86cb\u767d\u7684\u53ef\u80fd\u6027\u3002<\/span><\/span><\/p>\n


<\/span><\/p>\n

LNP-mRNA\u4e5f\u663e\u793a\u51fa\u4f5c\u4e3a\u75ab\u82d7\u7684\u6f5c\u5728\u5e94\u7528\u53ef\u80fd\u3002<\/span>Kranz\u7b49\u4eba\u7814\u7a76\u8868\u660e<\/span>LNP-mRNA\u5728\u6811\u7a81\u72b6\u7ec6\u80de\u514d\u75ab\u6cbb\u7597\u4e2d\uff0c\u53ef\u4ee5\u8bf1\u5bfc<\/span>DC\u7ec6\u80de\u4e2d\u6297\u539f\u7684\u8868\u8fbe\u3002\u6b64\u5916\uff0c\u8fd8\u53ef\u4ee5\u5728\u9ed1\u8272\u7d20\u7624\u3001\u7ed3\u76f4\u80a0\u764c\u548c\u80ba\u764c\u6a21\u578b\u4e2d\u8bf1\u5bfc\u4e86\u5f3a\u70c8\u7684\u6297\u80bf\u7624\u53cd\u5e94\uff0c\u8fd8\u5177\u6709\u5f88\u9ad8\u7684\u5b89\u5168\u6027\u548c\u8010\u53d7\u6027\u3002<\/span>Yin\u7b49\u4eba\u5229\u7528<\/span>LNP-CRISPR\u6280\u672f\u9776\u5411\u5c0f\u9f20\u7684<\/span>PCSK9\u57fa\u56e0\u6cbb\u7597\u9ad8\u80c6\u56fa\u9187\u8840\u75c7\uff0c\u5728\u4e00\u6b21\u6ce8\u5c04\u540e\u53ef\u4ee5\u5c06\u5c0f\u9f20\u7684\u80c6\u56fa\u9187\u964d\u4f4e<\/span>30~40%\u3002<\/span><\/span><\/p>\n


<\/span><\/strong><\/span><\/p>\n

5 \u603b\u7ed3<\/span><\/span><\/strong><\/span><\/h1>\n


<\/span><\/p>\n

\u53ef\u79bb\u5b50\u5316\u7684\u9633\u79bb\u5b50\u8102\u8d28\u5728<\/span>LNP-siRNA\u6cbb\u7597\u4e2d\u8d77\u5230\u4e86\u7684\u5173\u952e\u56e0\u7d20\u3002<\/span>MC3\u7b49\u8102\u8d28\u53ef\u4ee5\u5b9e\u73b0\u6709\u6548\u5730\u5305\u5c01<\/span>siRNA\uff0c\u5e26\u6765\u76f8\u5bf9\u4e2d\u6027\u7684<\/span>LNP\u8102\u8d28\u7eb3\u7c73\u9897\u7c92\uff0c\u800c\u5728\u5faa\u73af\u4e2d\u7684\u76f8\u5bf9\u4e2d\u6027\u7684\u8868\u9762\u7535\u8377\uff0c\u53ef\u4ee5\u4fc3\u8fdb<\/span>siRNA\u5728\u80de\u541e\u4e4b\u540e\u4ece\u5185\u8d28\u4f53\u9003\u9038\u5230\u7ec6\u80de\u8d28\u5185\u3002\u968f\u7740<\/span>FDA\u53ef\u80fd\u5728<\/span>2018\u5e74\u7684\u6279\u51c6\u4e0a\u5e02\u7684<\/span>Patisiran\uff0c\u8fd9\u7c7b\u6c89\u9ed8\u809d\u810f\u6c89\u9ed8\u81f4\u75c5\u57fa\u56e0\u7684\u836f\u7269\u7684\u6536\u5230\u5f88\u9ad8\u4e34\u5e8a\u671f\u671b\u3002\u53e6\u5916\uff0c\u542b\u6709\u53ef\u79bb\u5b50\u5316\u7684\u9633\u79bb\u5b50\u8102\u8d28\u7684<\/span>LNP\u4e5f\u4fc3\u8fdb<\/span>mRNA\u548c<\/span>CRISPR \/ Cas\u7b49\u5176\u4ed6\u57fa\u56e0\u6cbb\u7597\u7684\u5feb\u901f\u53d1\u5c55\u3002\u5c3d\u7ba1\uff0c\u4f8b\u5982\u6210\u672c\u9ad8\u4f01\u3001\u5185\u5728\u7684\u6bd2\u6027\u548c\u8131\u9776\u6548\u5e94\u7b49\u56f0\u96be\u4f9d\u65e7\u5b58\u5728\uff0c\u4f46\u8f7d\u9057\u4f20\u836f\u7269<\/span>LNP\u73b0\u5728\u53ef\u4ee5\u5b9e\u73b0\u809d\u7ec6\u80de\u4e2d\u51e0\u4e4e\u6240\u6709\u57fa\u56e0\u7684\u6572\u9664\uff0c\u8868\u8fbe\u6216\u7f16\u8f91\uff0c\u672a\u6765\u8fd8\u6709\u6709\u671b\u5ef6\u4f38\u81f3\u5176\u4ed6\u7ec4\u7ec7\u7684\u5e94\u7528\uff0c\u672a\u6765\u4e2a\u6027\u5316\u57fa\u56e0\u7597\u6cd5\u4f1a\u6709\u66f4\u91cd\u5927\u7a81\u7834\u3002<\/span><\/span><\/p>\n


<\/p>\n<\/p>\n


<\/p>\n

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\u59cb\u53d1\u4e8e\u5fae\u4fe1\u516c\u4f17\u53f7\uff1a \u7cfb\u7edf <\/p>\n<\/blockquote>\n<\/div>\n","protected":false},"excerpt":{"rendered":"

\u3010\u975e\u5e38\u611f\u8c22\u4f5c\u8005\u201c\u4e09\u4e03\u201d\u7684\u6295\u7a3f\u3011 \u8102\u8d28\u7eb3\u7c73\u7c92\u5b50\uff1a\u4fc3\u8fdb\u57fa\u56e0\u7597\u6cd5\u4ece\u6982\u5ff5\u5230\u4e34\u5e8a\u6548\u7528 \u51e0\u4e4e\u4efb\u4f55\u75be\u75c5\u90fd\u53ef\u4ee5\u901a\u8fc7\u6c89\u9ed8\u75c5\u7406\u6027\u57fa […]<\/p>\n","protected":false},"author":1,"featured_media":4685,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[2],"tags":[],"_links":{"self":[{"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/posts\/4684"}],"collection":[{"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/comments?post=4684"}],"version-history":[{"count":1,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/posts\/4684\/revisions"}],"predecessor-version":[{"id":4686,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/posts\/4684\/revisions\/4686"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/media\/4685"}],"wp:attachment":[{"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/media?parent=4684"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/categories?post=4684"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/tags?post=4684"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}