{"id":61001,"date":"2018-10-18T01:00:00","date_gmt":"2018-12-07T03:03:40","guid":{"rendered":"http:\/\/www.05921.net\/index.php\/2018\/12\/07\/18faf6f50e\/"},"modified":"2018-12-07T11:03:43","modified_gmt":"2018-12-07T03:03:43","slug":"18faf6f50e","status":"publish","type":"post","link":"https:\/\/www.05921.net\/index.php\/61001\/","title":{"rendered":"RNA\u836f\u7269-\u80bf\u7624\u514d\u75ab\u7684\u4e0b\u4e00\u4e2a\u98ce\u53e3\uff1f"},"content":{"rendered":"
\n

\u4f5c\u8005 l Timbersaw<\/span><\/strong><\/p>\n

\u7f16\u8f91 l \u7ec6\u80de\u623f\u95f4<\/span><\/strong><\/p>\n

\u8f6c\u8f7d\u81ea\uff1a<\/strong><\/span><\/span><\/p>\n

<\/span>
<\/h1>\n

\u4e00\u3001\u80cc\u666f<\/span><\/strong><\/h1>\n

2018\u5e74\u8bfa\u8d1d\u5c14\u751f\u7406\u5b66\u548c\u533b\u5b66\u5956\u9881\u7ed9\u4e86Allison\u6559\u6388\u548c\u672c\u5eb6\u4f51\u6559\u6388\uff0c\u4ee5\u8868\u5f70\u4ed6\u4eec\u5728\u80bf\u7624\u514d\u75ab\u7597\u6cd5\uff08Cancer Immunotherapy\uff09\u9886\u57df\u7684\u5f00\u521b\u6027\u5de5\u4f5c\uff0c\u4e5f\u8ba9\u5168\u4e16\u754c\u8d8a\u6765\u8d8a\u591a\u7684\u4eba\u8ba4\u8bc6\u5230\uff0c\u514d\u75ab\u7597\u6cd5\u5c06\u4e3a\u80bf\u7624\u6cbb\u7597\u5e26\u6765\u9769\u547d\u6027\u7684\u6539\u53d8\u3002<\/span><\/p>\n


<\/p>\n

\u5f53\u524d\uff0c\u80bf\u7624\u514d\u75ab\u7597\u6cd5\u7684\u821e\u53f0\u57fa\u672c\u88ab\u6297\u4f53\u548c\u7ec6\u80de\u7597\u6cd5\u5360\u636e\u3002PD-1\/PD-L1\u6297\u4f53\u548cCAR-T\u7597\u6cd5\u6210\u4e86\u6211\u4eec\u8033\u719f\u80fd\u8be6\u7684\u8bdd\u9898\uff0c\u90e8\u5206\u80bf\u7624\u75c5\u4eba\u7684\u751f\u6d3b\u8d28\u91cf\u5f97\u4ee5\u6539\u5584\uff0c\u751f\u5b58\u671f\u5f97\u5230\u5ef6\u957f\uff0c\u751a\u81f3\u5b9e\u73b0\u5f7b\u5e95\u6cbb\u6108\u3002\u7136\u800c\uff0c\u9700\u8981\u6307\u51fa\u7684\u662f\uff0c\u4ecd\u6709\u76f8\u5f53\u4e00\u90e8\u5206\u75c5\u4eba\u5bf9PD-1\/PD-L1\u6297\u4f53\u7597\u6cd5\u4e0d\u5e94\u7b54\u6216\u51fa\u73b0\u75be\u75c5\u590d\u53d1\uff0cCAR-T\u7597\u6cd5\u526f\u4f5c\u7528\u98ce\u9669\u9ad8\u3001\u9488\u5bf9\u5b9e\u4f53\u7624\u7684\u6548\u679c\u4e0d\u4f73\u3001\u9700\u8981\u79bb\u4f53\u6539\u9020\u75c5\u4eba\u81ea\u8eab\u7ec6\u80de\u4e14\u8fc7\u7a0b\u590d\u6742\uff0c\u6297\u4f53\u548c\u7ec6\u80de\u751f\u4ea7\u6210\u672c\u90fd\u5341\u5206\u9ad8\u6602\uff0c\u8fd9\u4e9b\u90fd\u662f\u6446\u5728\u6211\u4eec\u9762\u524d\u4e9f\u5f85\u89e3\u51b3\u7684\u95ee\u9898\u3002<\/span><\/p>\n


<\/p>\n

\u5236\u836f\u754c\u5df2\u7ecf\u5728\u8fdb\u884c\u5404\u79cd\u79ef\u6781\u7684\u5c1d\u8bd5\uff0c\u6210\u767e\u4e0a\u5343\u79cd\u57fa\u4e8ePD-1\/PD-L1\u6297\u4f53\u7684\u836f\u7269\u8054\u7528\u7b56\u7565\uff0c\u5982\u901a\u7528\u578b\uff08off-the-shelf\uff09CAR-T\uff0cRNA\u836f\u7269\uff0c\u80bf\u7624\u591a\u80bd\u75ab\u82d7\u7b49\u5404\u79cd\u65b0\u6280\u672f\u3001\u65b0\u9776\u70b9\u3001\u65b0\u6cbb\u7597\u7b56\u7565\u4e0d\u65ad\u6d8c\u73b0\u3002\u672c\u6587\u5c06\u91cd\u70b9\u5173\u6ce8\u80bf\u7624\u514d\u75ab\u7597\u6cd5\u7684\u65b0\u70ed\u70b9\u2014RNA\u836f\u7269\uff0c\u4ecb\u7ecdRNA\u836f\u7269\u7c7b\u578b\u548c\u7ade\u4e89\u4f18\u52bf\uff0c\u4e34\u5e8a\u7ed3\u679c\u548c\u76f8\u5173\u4f01\u4e1a\uff0c\u4ea7\u4e1a\u74f6\u9888\u4ee5\u53ca\u53d1\u5c55\u7b56\u7565\u3002<\/span><\/p>\n

 <\/span><\/p>\n

\u4e8c\u3001RNA\u836f\u7269\u4e0e\u80bf\u7624\u514d\u75ab<\/span><\/strong><\/h1>\n


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

2.1 RNA\u836f\u7269\u603b\u89c8<\/span><\/strong><\/h2>\n

\u63d0\u8d77RNA\uff08Ribonucleic Acid\uff0c\u6838\u7cd6\u6838\u9178\uff09\uff0c\u6211\u4eec\u518d\u719f\u6089\u4e0d\u8fc7\u7684\u5c31\u662f\u4e2d\u5fc3\u6cd5\u5219\u7684\u91cd\u8981\u4e00\u73af\u2014mRNA\uff08\u4fe1\u4f7fRNA\uff09\u3002\u4f46\u5176\u5b9e\u9664\u4e86\u53ef\u4ee5\u4f5c\u4e3a\u86cb\u767d\u7ffb\u8bd1\u6a21\u677f\u7684mRNA\u4e4b\u5916\uff0c\u8fd8\u6709\u591a\u79cd\u7c7b\u578bRNA\u5728\u751f\u7269\u5b66\u8fc7\u7a0b\u4e2d\u8d77\u5230\u91cd\u8981\u4f5c\u7528\uff0c\u5982\u56fe1\u6240\u793a\uff1a<\/span><\/p>\n

    \n
  • \n

    \u7ed3\u6784\u578bRNA\uff0c\u5982rRNA\u3001tRNA\u3001snRNA\uff08\u5c0f\u578b\u6838RNA\uff09<\/span><\/p>\n<\/li>\n

  • \n

    \u8c03\u8282\u5185\u6e90\u6027mRNA\u8868\u8fbe\u7684\u5e72\u6270RNA\uff08RNAi\uff09\uff0c\u5982siRNA\u3001miRNA\u3001piRNA<\/span><\/p>\n<\/li>\n

  • \n

    \u8d77\u5230\u9e70\u67b6\uff08scaffolding\uff09\u529f\u80fd\u7684\u957f\u94fe\u975e\u7f16\u7801RNA\uff0c\u5373lncRNA<\/span><\/p>\n<\/li>\n

  • \n

    \u6784\u6210\u67d0\u4e9b\u75c5\u6bd2\u57fa\u56e0\u7ec4\u7684RNA\uff0c\u5373viral RNA<\/span><\/p>\n<\/li>\n

  • \n

    \u6709\u50ac\u5316\u6d3b\u6027\u7684RNA\uff0c\u5373Ribozymes<\/span><\/p>\n<\/li>\n<\/ul>\n

    \"RNA\u836f\u7269-\u80bf\u7624\u514d\u75ab\u7684\u4e0b\u4e00\u4e2a\u98ce\u53e3\uff1f\"<\/p>\n

    \u25b2\u56fe1. \u4e0d\u540cRNA\u4e9a\u578b\u548c\u76f8\u5173\u529f\u80fd<\/span>[1]<\/span><\/strong><\/p>\n

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

    \u57fa\u4e8eRNA\u5f00\u53d1\u7684\u6cbb\u7597\u6027\u836f\u7269\u5728\u9776\u70b9\u53ef\u53ca\u6027\u3001\u514d\u75ab\u539f\u6027\u3001\u7ec4\u7ec7\u900f\u8fc7\u6027\u3001\u836f\u7269\u4ee3\u8c22\u3001\u751f\u4ea7\u8d28\u63a7\u548c\u6210\u672c\u7b49\u65b9\u9762\u90fd\u6709\u4e00\u5b9a\u4f18\u52bf\u3002\u5236\u836f\u754c20\u591a\u5e74\u6765\u4e00\u76f4\u5728\u4e0d\u65ad\u5c1d\u8bd5RNA\u836f\u7269\u7684\u5f00\u53d1\u548c\u5de5\u827a\u4f18\u5316\uff0c\u5df2\u6709\u8fd1200\u4e2a\u9879\u76ee\u8fdb\u5165\u4e34\u5e8a\u8bd5\u9a8c\u9636\u6bb5\uff0c\u7528\u4e8e\u6cbb\u7597\u764c\u75c7\u3001\u4f20\u67d3\u75c5\u3001\u6fc0\u7d20\u6027\u75be\u75c5\u751a\u81f3\u4ea8\u5ef7\u987f\u75c5\u7b49\u795e\u7ecf\u6027\u75be\u75c5\u3002\u5904\u4e8e\u4e34\u5e8a\u5f00\u53d1\u7684RNA\u836f\u7269\u4e2d\uff0c\u8f83\u4e3a\u6210\u719f\u7684\u6709\u53cd\u4e49RNA\uff0cRNAi\uff0cRNA\u75ab\u82d7\uff0cRNA Aptamer\uff08\u9002\u914d\u4f53\uff09\uff0cRibozymes\u7b49\u3002\u5f53\u7136\u6211\u4eec\u4e5f\u4e0d\u80fd\u5fd8\u4e86\u8fd1\u5e74\u6765\u975e\u5e38\u706b\u70ed\u7684CRISPR-gRNA\uff08guide RNA\uff09\u3002<\/span><\/p>\n


    <\/p>\n

    RNA\u836f\u7269\u5ba1\u6279\u5927\u4e8b\u8bb0\uff1a<\/span><\/p>\n

      \n
    • \n

      2016\u5e749\u6708\uff0cFDA\u6279\u51c6Sarepta Therapeutics\u516c\u53f8\u7684\u53cd\u4e49RNA\uff08\u53ef\u4e0emRNA\u4e92\u8865\u7684RNA\u5206\u5b50\uff0c\u53ef\u6291\u5236mRNA\u7684\u7ffb\u8bd1\u8fc7\u7a0b\uff09\u836f\u7269Eteplirsen\uff0c\u7528\u4e8e\u6cbb\u7597\u5916\u663e\u5b5051\u8df3\u8dc3\u578b\u675c\u6c0f\u808c\u8425\u517b\u4e0d\u826f\uff08DMA\uff09\uff1b<\/span><\/p>\n<\/li>\n

    • \n

      2018\u5e748\u6708\uff0c\u7f8e\u56fdFDA\u6279\u51c6Alnylam\u516c\u53f8\u7684RNAi\u7597\u6cd5Patisiran\uff0c\u7528\u4e8e\u9057\u4f20\u6027\u8f6c\u7532\u72b6\u817a\u7d20\u86cb\u767d\u6dc0\u7c89\u6837\u53d8\u6027\uff08hATTR\uff09\uff0c<\/span>\u4f7f\u4e4b\u6210\u4e3a\u9996\u4e2a\u83b7\u6279\u4e0a\u5e02\u7684RNAi\u7597\u6cd5<\/span><\/strong><\/span>\u3002<\/span><\/p>\n<\/li>\n

    • \n

      2018\u5e7410\u6708\uff0c\u7f8e\u56fdFDA\u6279\u51c6Ionis Pharmaceuticals\u548c\u5176\u4e0b\u5c5e\u516c\u53f8Akcea Therapeutics\u8054\u5408\u5f00\u53d1\u7684\u53cd\u4e49\u5be1\u6838\u82f7\u9178\u836f\u7269Tegsedi\uff08Inotersen\uff09\u4e0a\u5e02\uff0c\u7528\u4e8e\u6cbb\u7597\u9057\u4f20\u6027\u8f6c\u7532\u72b6\u817a\u7d20\u86cb\u767d\u6dc0\u7c89\u6837\u53d8\u6027\uff08hATTR\uff09\u60a3\u8005\u7684\u591a\u53d1\u6027\u795e\u7ecf\u75c5\uff08Polyneuropathy\uff09\u3002<\/span><\/p>\n<\/li>\n<\/ul>\n

       <\/span><\/p>\n

      \u53cd\u4e49RNA\uff0cRNAi\uff0c\u4ee5\u53caCRISPR\/gRNA\u591a\u5e94\u7528\u4e8e\u81f4\u75c5\u56e0\u7d20\u8f83\u4e3a\u5355\u4e00\u7684\u75be\u75c5\uff0c\u800c\u80bf\u7624\u662f\u9ad8\u5ea6\u5f02\u8d28\u7684\uff0c\u4e14\u81f4\u75c5\u673a\u7406\u5341\u5206\u590d\u6742\u3002\u56e0\u6b64\uff0c\u9488\u5bf9\u80bf\u7624\u6cbb\u7597\uff0cRNA\u836f\u7269\u7684\u5f00\u53d1\u7b56\u7565\u4e3b\u8981\u96c6\u4e2d\u5728\u4e24\u4e2a\u65b9\u9762\uff1a1\uff09\u6fc0\u6d3b\u673a\u4f53\u7684\u56fa\u6709\u514d\u75ab\uff08Innate immunity\uff09\u548c\u83b7\u5f97\u6027\u514d\u75ab\uff08Adaptive immunity\uff09\u4ece\u800c\u6740\u4f24\u80bf\u7624\uff0c\u5373RNA\u75ab\u82d7\uff1b2\uff09\u7ed3\u5408\u5e76\u8c03\u8282\u514d\u75ab\u6291\u5236\u6027\u6216\u6fc0\u52a8\u6027\u53d7\u4f53\u4ece\u800c\u4fc3\u8fdb\u6548\u5e94\u7ec6\u80de\u7684\u6740\u4f24\u4f5c\u7528\uff0c\u5373RNA\u9002\u914d\u4f53\u3002<\/span><\/p>\n

       <\/span><\/p>\n

      2.2 RNA\u80bf\u7624\u75ab\u82d7\uff08RNA Cancer Vaccine\uff09<\/span><\/strong><\/h2>\n

      \u5916\u6e90\u6027RNA\u80fd\u591f\u5f15\u53d1\u673a\u4f53\u7684\u56fa\u6709\u514d\u75ab\u548c\u83b7\u5f97\u6027\u514d\u75ab\u53cd\u5e94\u3002\u5728\u80bf\u7624\u6cbb\u7597\u4e2d\u5229\u7528\u8fd9\u4e00\u673a\u7406\uff0c\u4ee5\u75ab\u82d7\u7684\u5f62\u5f0f\u5f15\u5165\u5916\u6e90\u6027RNA\uff0c\u53ef\u4ee5\u4fc3\u8fdb\u708e\u75c7\u7ec6\u80de\u56e0\u5b50\u53ca\u5e72\u6270\u7d20\u7684\u91ca\u653e\uff0c\u6fc0\u6d3bNK\u3001\u5de8\u566c\u7ec6\u80de\u3001\u6548\u5e94T\u7ec6\u80de\uff0c\u5c06\u6ca1\u6709\u514d\u75ab\u7ec6\u80de\u6d78\u6da6\u7684”\u51b7\u80bf\u7624\u201d\u53d8\u4e3a\u201c\u70ed\u80bf\u7624\u201d\uff0c\u4fc3\u8fdb\u514d\u75ab\u7cfb\u7edf\u5bf9\u764c\u7ec6\u80de\u7684\u6740\u4f24\u4f5c\u7528\uff0c\u4e5f\u80fd\u534f\u540c\u63d0\u9ad8\u514d\u75ab\u68c0\u67e5\u70b9\u6291\u5236\u5242\u6297\u4f53\u7684\u7597\u6548\uff0c\u5373\u5728\u7ed9\u514d\u75ab\u7cfb\u7edf\u201c\u677e\u5239\u8f66\u201d\u7684\u540c\u65f6\u201c\u8e29\u6cb9\u95e8\u201d\uff0c\u4ece\u800c\u8fdb\u4e00\u6b65\u589e\u5f3a\u6297\u80bf\u7624\u514d\u75ab\u53cd\u5e94\u3002\u5177\u4f53\u60c5\u51b5\u53ef\u5206\u4e3a\u4e24\u7c7b\uff1a<\/span><\/p>\n

       <\/span><\/p>\n

      RNA\u75ab\u82d7\u4e0e\u56fa\u6709\u514d\u75ab\u3002<\/span><\/strong>\u56fa\u6709\u514d\u75ab\u53c8\u79f0\u975e\u7279\u5f02\u6027\u514d\u75ab\uff0c\u662f\u673a\u4f53\u8bc6\u522b\u75c5\u539f\u4f53\u6216\u201c\u635f\u4f24\u4e8b\u4ef6\u201d\u4fe1\u53f7\u7684\u91cd\u8981\u9632\u5fa1\u673a\u5236\u3002\u56fa\u6709\u514d\u75ab\u7ec6\u80de\uff08\u5982DC\uff0cNK\uff0c\u5de8\u566c\u7ec6\u80de\u7b49\uff09\u4e0a\u7684\u6a21\u5f0f\u8bc6\u522b\u53d7\u4f53\uff08PRR\uff09\u53ef\u4ee5\u5feb\u901f\u8bc6\u522b\u75c5\u539f\u4f53\u76f8\u5173\u5206\u5b50\u6a21\u5f0f\uff08PAMP\uff09\u548c\u635f\u4f24\u76f8\u5173\u5206\u5b50\u6a21\u5f0f\uff08DAMP\uff09\uff08\u6ce8\uff1a\u5916\u6e90\u6027RNA\u662f\u4e00\u7c7b\u91cd\u8981\u7684PAMP\/DAMP\uff09\uff0c\u901a\u8fc7\u8c03\u8282\u5e72\u6270\u7d20\uff08IFN\uff09\u53ca\u76f8\u5173\u57fa\u56e0\u8868\u8fbe\uff0c\u4fc3\u8fdb\u708e\u6027\u7ec6\u80de\u56e0\u5b50\u8868\u8fbe\u7b49\u4e00\u7cfb\u5217\u7ec6\u80de\u4fe1\u53f7\u8f6c\u5bfc\u8fc7\u7a0b\uff0c\u5b9e\u73b0\u5bf9\u5f02\u6e90\u7269\u8d28\u7684\u62b5\u5fa1\u548c\u6e05\u9664\uff0c\u5982\u56fe2\u3002\u4f46\u9700\u8981\u6307\u51fa\u7684\u662f\uff0c\u5916\u6e90\u6027RNA\u5f15\u53d1\u7684\u56fa\u6709\u514d\u75ab\u53cd\u5e94\u53ef\u80fd\u901a\u8fc7\u5e72\u6270\u7d20\u4fe1\u53f7\u4e0b\u8c03mRNA\u7684\u7ffb\u8bd1\u6548\u7387\uff0c\u5f71\u54cdmRNA\u75ab\u82d7\u5bf9\u83b7\u5f97\u6027\u514d\u75ab\u53cd\u5e94\u7684\u6fc0\u6d3b\uff08\u4e0b\u6587\u4ecb\u7ecd\uff09\uff0c\u56e0\u6b64\uff0c\u5173\u4e8e\u662f\u5426\u9700\u8981\u5bf9RNA\u8fdb\u884c\u5316\u5b66\u4fee\u9970\u4ee5\u964d\u4f4e\u5176\u5f15\u53d1\u7684\u56fa\u6709\u514d\u75ab\u53cd\u5e94\uff0c\u4ecd\u5f85RNA\u75ab\u82d7\u9886\u57df\u8fdb\u4e00\u6b65\u7814\u7a76\u6765\u6743\u8861\u5229\u5f0a\u3002<\/span><\/p>\n

      \"RNA\u836f\u7269-\u80bf\u7624\u514d\u75ab\u7684\u4e0b\u4e00\u4e2a\u98ce\u53e3\uff1f\"<\/p>\n

      \u25b2\u56fe2. \u56fa\u6709\u514d\u75ab\u7cfb\u7edf\u8bc6\u522b\u5916\u6e90RNA<\/span>[1]<\/span><\/strong><\/p>\n


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

      \u805a\u808c\u80de\u82f7\u9178\uff08Poly I\uff1aC\uff09\u4e00\u79cd\u5408\u6210\u7684\u53cc\u94feRNA\uff08dsRNA\uff09\uff0c\u9ad8\u6548\u5e72\u6270\u7d20\u8bf1\u5bfc\u5242\uff0c\u6709\u5e7f\u8c31\u6297\u75c5\u6bd2\u4f5c\u7528\uff0c\u589e\u5f3a\u514d\u75ab\u548c\u6297\u80bf\u7624\u4f5c\u7528\u3002\u8fd9\u7c7bRNA\u836f\u7269\u4e3b\u8981\u901a\u8fc7\u6fc0\u6d3b\u56fa\u6709\u514d\u75ab\u53d7\u4f53Toll\u6837\u53d7\u4f533\uff08TLR3\uff09\u548c\u9ed1\u8272\u7d20\u7624\u5206\u5316\u76f8\u5173\u86cb\u767d5\uff08MDA5\uff09\uff0c\u5f15\u53d1\u514d\u75ab\u53cd\u5e94\uff0c\u4ece\u4ee5\u524d\u7684\u6297\u75c5\u6bd2\/\u6297\u80bf\u7624\u75ab\u82d7\u7684\u4f50\u5242\uff08adjuvant\uff09\uff0c\u9010\u6b65\u88ab\u5f00\u53d1\u4e3a\u8bf1\u5bfc\u6297\u80bf\u7624\u514d\u75ab\u53cd\u5e94\u7684\u5355\u4e00\u7597\u6cd5\u3002BO\u2011112\u662f\u897f\u73ed\u7259Bioncotech Therapeutics\u516c\u53f8\u7684\u6838\u5fc3\u8d44\u4ea7\uff0c\u662f\u4e00\u79cd\u7531Poly I\uff1aC\u548c\u805a\u4e59\u70ef\u4e9a\u80fa\uff08PEI\uff09\u7ec4\u6210\u7684\u590d\u5408dsRNA\u3002BO\u2011112\u901a\u8fc7\u8bf1\u5bfc\u81ea\u566c\uff08Autophagy\uff09\u5f15\u53d1\u764c\u7ec6\u80de\u7684\u7ec6\u80de\u6bd2\u6548\u5e94\uff0c\u76ee\u524d\u6b63\u5728I\u671f\u4e34\u5e8a\u8bd5\u9a8c\u68c0\u6d4b\u4e0ePD-1\u6297\u4f53\u8054\u7528\u7597\u6548\uff08ClinicalTrials.gov\uff1aNCT02828098\uff09\u3002<\/span><\/p>\n

       <\/span><\/p>\n

      RNA\u75ab\u82d7\u4e0e\u83b7\u5f97\u6027\u514d\u75ab\u3002<\/span><\/strong>\u83b7\u5f97\u6027\u514d\u75ab\u53c8\u79f0\u7279\u5f02\u6027\u514d\u75ab\uff0c\u662f\u673a\u4f53\u53d7\u5230\u7279\u5b9a\u6297\u539f\u523a\u6fc0\u540e\u5f62\u6210\u7684\uff0c\u4ec5\u9488\u5bf9\u8be5\u6297\u539f\u7684\u514d\u75ab\u53cd\u5e94\uff0c\u4e3b\u8981\u6709T\u7ec6\u80de\uff08\u7ec6\u80de\u514d\u75ab\uff09\u548cB\u7ec6\u80de\uff08\u4f53\u6db2\u514d\u75ab\uff09\u53c2\u4e0e\u3002B\u7ec6\u80de\u4ecb\u5bfc\u7684\u4f53\u6db2\u514d\u75ab\u4e3b\u8981\u4e0e\u6297\u4f53\u4ea7\u751f\u76f8\u5173\uff0c\u800cT\u7ec6\u80de\u4ecb\u5bfc\u7684\u7ec6\u80de\u514d\u75ab\u5219\u6709\u7740\u66f4\u76f4\u63a5\u7684\u6297\u80bf\u7624\u6548\u5e94\u3002\u6297\u539f\u80bd\u9700\u8981\u7ecf\u7531\u6297\u539f\u5448\u9012\u7ec6\u80de\uff08APC\uff0c\u6700\u4e3b\u8981\u662fDC\u7ec6\u80de\uff09\u5904\u7406\uff0c\u5e76\u901a\u8fc7\u4e3b\u8981\u7ec4\u7ec7\u76f8\u5bb9\u6027\u6297\u539f\u590d\u5408\u4f53\uff08MHC\uff09\u5448\u9012\u7ed9T\u7ec6\u80de\u53d7\u4f53\uff08TCR\uff09\uff0c\u8fdb\u800c\u6fc0\u53d1T\u7ec6\u80de\u514d\u75ab\u6548\u5e94\u3002\u4eba\u5de5\u5408\u6210\u7684\u80bf\u7624\u591a\u80bd\u75ab\u82d7\u5df2\u9010\u6e10\u8fdb\u5165\u4e34\u5e8a\u7814\u7a76\u9636\u6bb5\uff0c\u5e76\u5728\u9ed1\u8272\u7d20\u7624\u7b49\u5bcc\u96c6\u57fa\u56e0\u7a81\u53d8\u7684\u80bf\u7624\u4e2d\u521d\u6b65\u663e\u793a\u51fa\u79ef\u6781\u7597\u6548\u3002<\/span><\/p>\n

       <\/span><\/p>\n

      \u4f46\u503c\u5f97\u6ce8\u610f\u7684\u662f\uff0c\u6709\u6587\u732e\u62a5\u9053\u79f0\uff0c\u591a\u80bd\u75ab\u82d7\u4e3b\u8981\u901a\u8fc7APC\u7684\u5185\u541e\u4f53\uff08Endosome\uff09\u5904\u7406\u540e\u7ecf\u7531II\u578bMHC\u5448\u9012\u5e76\u6fc0\u6d3bCD4\u9633\u6027T\u7ec6\u80de\uff1b\u800c\u7531RNA\u75ab\u82d7\u7f16\u7801\u7684\u6297\u539f\u80bd\u4e3b\u8981\u4ea7\u751f\u4e8e\u7ec6\u80de\u8d28\u5185\uff0c\u7ecf\u7531I\u578bMHC\u5448\u9012\u5e76\u6fc0\u6d3b\u66f4\u5177\u80bf\u7624\u6740\u4f24\u4f5c\u7528\u7684CD8\u9633\u6027T\u7ec6\u80de\u3002\u56e0\u6b64\uff0cRNA\u53ef\u4ee5\u4f5c\u4e3a\u5f00\u53d1\u80bf\u7624\u6cbb\u7597\u6027\u75ab\u82d7\u7684\u65b0\u9009\u62e9\u3002<\/span><\/p>\n

       <\/span><\/p>\n

      \u5f00\u53d1\u80bf\u7624\u6cbb\u7597\u578bRNA\u75ab\u82d7\uff08\u7531\u4e8e\u9700\u8981\u7f16\u7801\u6297\u539f\u80bd\uff0c\u57fa\u672c\u5747\u4e3amRNA\u75ab\u82d7\uff09\uff0c\u9700\u8981\u89e3\u51b3\u4e24\u4e2a\u4e3b\u8981\u95ee\u9898\uff1a1. \u9009\u62e9\u5408\u9002\u7684\u76ee\u6807\u6297\u539f\uff1b2. \u9009\u62e9\u5408\u9002\u7684\u9012\u9001\u7b56\u7565\uff08\u7ed9\u836f\u65b9\u5f0f\u3001\u8f7d\u4f53\u3001\u4f50\u5242\u7b49\uff09\u3002<\/strong><\/span><\/p>\n

       <\/span><\/p>\n

      1 \u6297\u539f\u7684\u9009\u62e9\u3002<\/span><\/strong>\u524d\u4e9b\u5e74\u7684\u80bf\u7624\u75ab\u82d7\u4e3b\u8981\u9488\u5bf9\u80bf\u7624\u76f8\u5173\u6297\u539f\uff08Tumor-associated antigens\uff0cTAA\uff09\uff0c\u4f46\u7531\u4e8e\u8fd9\u4e9b\u6297\u539f\u4e5f\u4f1a\u5728\u6b63\u5e38\u7ec4\u7ec7\u8868\u8fbe\uff0c\u6700\u7ec8\u53ef\u80fd\u56e0\u514d\u75ab\u8010\u53d7\u964d\u4f4e\u75ab\u82d7\u7597\u6548\uff0c\u6216\u662f\u5f15\u53d1\u4e25\u91cd\u526f\u53cd\u5e94\u5bfc\u81f4\u81ea\u8eab\u514d\u75ab\u75be\u75c5\u3002\u56e0\u6b64\uff0c\u8fd1\u5e74\u6765\u7684\u80bf\u7624\u75ab\u82d7\u5f00\u53d1\u8d8a\u6765\u8d8a\u805a\u7126\u4e8e\u4e2a\u6027\u5316\u7684\uff08Personalized\uff09\u80bf\u7624\u7279\u5f02\u6027\u6297\u539f\uff08Tumor-specific antigen\uff0cTSA\uff09\uff0c\u4e5f\u7ecf\u5e38\u88ab\u79f0\u4f5c\u80bf\u7624\u65b0\u751f\u6297\u539f\uff08Neo-antigens\uff09\u3002\u90a3\u4e48\u5982\u4f55\u627e\u5230\u67d0\u4e2a\u75c5\u4eba\u7684neo-antigens\u5462\uff1f\u7b80\u800c\u8a00\u4e4b\uff0c\u7531\u4e8e\u80bf\u7624\u7684\u5f02\u8d28\u6027\uff0c\u4e0d\u540c\u75c5\u4eba\u7684\u80bf\u7624\u57fa\u56e0\u7a81\u53d8\u4e0d\u5c3d\u76f8\u540c\uff0c\u5176\u4e2d\u5f88\u591a\u7a81\u53d8\u5c06\u7f16\u7801\u4ea7\u751f\u4ec5\u5728\u80bf\u7624\u90e8\u4f4d\u8868\u8fbe\u7684\u6297\u539f\uff0c\u901a\u8fc7\u6bd4\u5bf9\u67d0\u4e00\u75c5\u4eba\u6b63\u5e38\u7ec4\u7ec7\uff08\u4e00\u822c\u7528\u5916\u5468\u8840PBMC\u6216\u764c\u65c1\u7ec4\u7ec7\uff09\u4e0e\u80bf\u7624\u7ec4\u7ec7\u7684\u8f6c\u5f55\u7ec4\uff0c\u7ed3\u5408\u751f\u7269\u4fe1\u606f\u5b66\u5206\u6790\u4fbf\u53ef\u7b5b\u9009\u80bf\u7624\u7279\u5f02\u6027\u6297\u539f\uff0c\u9884\u6d4b\u4e0eMHC\uff08\u4eba\u7c7bHLA\uff09\u7ed3\u5408\u6700\u4f73\u7684\u5e8f\u5217\uff0c\u518d\u901a\u8fc7\u4f53\u5185\u4f53\u5916\u6a21\u578b\u8bd5\u9a8c\u4ece\u8fd9\u4e9b\u5e8f\u5217\u4e2d\u627e\u51fa\u80fd\u6fc0\u53d1\u663e\u8457\u6297\u80bf\u7624\u514d\u75ab\u53cd\u5e94\u7684\u4e00\u4e9b\u6297\u539f\u5f00\u53d1\u75ab\u82d7\u3002mRNA\u548c\u591a\u80bd\u75ab\u82d7\u7684\u57fa\u672c\u6d41\u7a0b\u5927\u81f4\u76f8\u540c\uff0c\u5982\u56fe3\u6240\u793a\u3002\u4f46mRNA\u75ab\u82d7\u7684\u9012\u9001\u65b9\u5f0f\u66f4\u52a0\u591a\u6837\u5316\uff0c\u4e0b\u6587\u4ecb\u7ecd\u3002<\/span><\/p>\n

      \"RNA\u836f\u7269-\u80bf\u7624\u514d\u75ab\u7684\u4e0b\u4e00\u4e2a\u98ce\u53e3\uff1f\"<\/p>\n

      \u25b2\u56fe3. \u4e2a\u4f53\u5316\u80bf\u7624mRNA\u75ab\u82d7\u5f00\u53d1\u6d41\u7a0b[1]<\/span><\/strong><\/span> <\/p>\n

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

      2 \u9012\u9001\u7b56\u7565\u7684\u9009\u62e9\u3002<\/span><\/strong>\u5728\u660e\u786emRNA\u75ab\u82d7\u7684\u9776\u6297\u539f\u540e\uff0c\u8981\u89e3\u51b3\u662f\u5426\u5bf9mRNA\u8fdb\u884c\u5316\u5b66\u4fee\u9970\uff0c\u4f7f\u7528\u4f55\u79cd\u8f7d\u4f53\uff0c\u4ee5\u53ca\u9009\u62e9\u4f55\u79cd\u7ed9\u836f\u65b9\u5f0f\u8fd9\u51e0\u4e2a\u95ee\u9898\uff1a<\/span><\/p>\n


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

        \n
      • \n

        \u5316\u5b66\u4fee\u9970mRNA\u3002<\/span><\/strong>\u6709\u4e34\u5e8a\u524d\u7814\u7a76\u663e\u793a\uff0c\u52a0\u5165\u7ecf\u5316\u5b66\u4fee\u9970\u7684\u78b1\u57fa\u5982\u5047\u5c3f\u82f7\u62161-\u7532\u57fa\u5047\u5c3f\u82f7\u7b49\uff0c\u53ef\u4ee5\u6291\u5236RNA\u56fa\u6709\u514d\u75ab\u5f15\u8d77\u7684\u7ffb\u8bd1\u6291\u5236\uff0c\u4fc3\u8fdb\u6297\u539f\u80bd\u8868\u8fbe\u53caT\u7ec6\u80de\u514d\u75ab\u7684\u6fc0\u6d3b\u3002\u4f46\u4e5f\u6709\u62a5\u9053\u79f0\u672a\u7ecf\u5316\u5b66\u4fee\u9970\u7684RNA\u53ef\u4ee5\u7ffb\u8bd1\u51fa\u66f4\u591a\u7684\u6297\u539f\u80bd\u3002\u8fd9\u4e9b\u5dee\u5f02\u53ef\u80fd\u6765\u81ea\u8bd5\u9a8c\u7cfb\u7edf\u7684\u5dee\u522b\u3002\u53e6\u5916\uff0c\u5e26\u6b63\u7535\u7684\u9c7c\u7cbe\u86cb\u767d\u4fee\u9970\u7684RNA\u53ef\u4ee5\u907f\u514d\u88ab\u8840\u6e05RNA\u9176\u6c34\u89e3\uff0c\u4ece\u800c\u63d0\u9ad8\u7a33\u5b9a\u6027\uff0c\u4f46\u8be5\u7b56\u7565\u7684\u4f53\u5185\u6d3b\u6027\u6709\u5f85\u4f18\u5316\u63d0\u9ad8\u3002\u6b63\u5982\u4e0a\u6587\u2018RNA\u75ab\u82d7\u4e0e\u56fa\u6709\u514d\u75ab\u2019\u6bb5\u843d\u6240\u6307\u51fa\u7684\uff0c\u5b66\u672f\u754c\u548c\u5de5\u4e1a\u754c\u8fd8\u9700\u8fdb\u4e00\u6b65\u7814\u7a76\u662f\u5426\u5e94\u5bf9RNA\u8fdb\u884c\u5316\u5b66\u4fee\u9970\u4ee5\u589e\u5f3aRNA\u75ab\u82d7\u529f\u6548\u3002<\/span><\/p>\n


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

      • \n

        mRNA\u75ab\u82d7\u8f7d\u4f53\u3002<\/span><\/strong>\u5b66\u672f\u7814\u7a76\u4e2d\u7ecf\u5e38\u7528\u5230\u7684\u9633\u79bb\u5b50\u591a\u805a\u7269\u6216\u8102\u8d28\u4f53\uff0c\u5982TransIT-mRNA(Mirus BioLLC)\u548cLipofectamine (Invitrogen)\uff0c\u4f5c\u4e3aRNA\u8f6c\u67d3\u7684\u8f7d\u4f53\u6548\u679c\u660e\u663e\uff0c\u4f46\u4e0a\u8ff0\u8f7d\u4f53\u7684\u4f53\u5185\u8bd5\u9a8c\u6d3b\u6027\u5e76\u4e0d\u5982\u4f53\u5916\u8bd5\u9a8c\u90a3\u6837\u663e\u8457\uff0c\u540c\u65f6\u6bd2\u6027\u53ef\u80fd\u8f83\u5927\u3002\u4e00\u4e9b\u65b0\u578b\u7684\u9633\u79bb\u5b50\u591a\u805a\u7269\u6216\u8102\u8d28\u4f53\uff0c\u5982\u6811\u72b6\u805a\u5408\u7269\uff08dendrimer\uff09\u548c\u8102\u8d28\u4f53\u7eb3\u7c73\u9897\u7c92\uff08LNPs\uff09\u6210\u4e3a\u4e86\u5e94\u7528\u6700\u5e7f\u6cdb\u7684mRNA\u75ab\u82d7\u8f7d\u4f53\u7c7b\u578b\u3002\u5176\u4e2dLNPs\u7684\u5e7f\u6cdb\u5e94\u7528\u4e5f\u5f97\u76ca\u4e8esiRNA\u836f\u7269\u7684\u5feb\u901f\u53d1\u5c55\u3002 <\/span>
        <\/p>\n<\/li>\n<\/ul>\n

        \"RNA\u836f\u7269-\u80bf\u7624\u514d\u75ab\u7684\u4e0b\u4e00\u4e2a\u98ce\u53e3\uff1f\"<\/p>\n

        \u25b2\u56fe4. mRNA\u75ab\u82d7\u7684\u4e3b\u8981\u8f7d\u4f53\u7c7b\u578b<\/span>[2]<\/span><\/strong><\/p>\n

        \uff08a. \u65e0\u4fee\u9970mRNA\uff1bb. \u7535\u7a7f\u5b54\u9012\u9001\u65e0\u4fee\u9970mRNA\uff1bc. \u9c7c\u7cbe\u86cb\u767d\u4fee\u9970\u7684mRNA\uff1bd. \u9633\u79bb\u5b50\u7eb3\u7c73\u4e73\u6db2\u8f7d\u4f53\uff1be. \u6811\u72b6\u805a\u5408\u7269\u7eb3\u7c73\u9897\u7c92\u8f7d\u4f53\uff1bf. \u8102\u8d28\u4f53\u9012\u9001\u9c7c\u7cbe\u86cb\u767d\u4fee\u9970\u7684mRNA\uff1bg.\u9633\u79bb\u5b50\u805a\u5408\u7269\u8f7d\u4f53\uff1bh. \u9633\u79bb\u5b50\u805a\u5408\u7269\u8102\u8d28\u4f53\u8f7d\u4f53\uff1bi. \u591a\u7cd6\u9897\u7c92\u8f7d\u4f53\uff1bj. \u9633\u79bb\u5b50\u8102\u8d28\u4f53\u7eb3\u7c73\u9897\u7c92\u8f7d\u4f53\uff1bk. \u878d\u5408\u80c6\u56fa\u9187\u7684\u9633\u79bb\u5b50\u8102\u8d28\u4f53\u7eb3\u7c73\u9897\u7c92\u8f7d\u4f53\uff1bl. PEG\u4fee\u9970\u7684\uff0c\u878d\u5408\u80c6\u56fa\u9187\u7684\u9633\u79bb\u5b50\u8102\u8d28\u4f53\u7eb3\u7c73\u9897\u7c92\u8f7d\u4f53\uff09<\/span><\/p>\n


        <\/p>\n

          \n
        • \n

          mRNA\u75ab\u82d7\u7ed9\u836f\u65b9\u5f0f\u3002<\/span><\/strong>mRNA\u75ab\u82d7\u7ed9\u836f\u65b9\u5f0f\u4e3b\u8981\u6709\u4e24\u79cd\uff1a1\uff09\u76f4\u63a5\u6ce8\u5c04\uff0c\u9014\u5f84\u5305\u62ec\u6dcb\u5df4\u7ed3\u5185\u6ce8\u5c04\u3001\u808c\u8089\u6ce8\u5c04\u3001\u76ae\u5185\u6ce8\u5c04\u3001\u9759\u8109\u6ce8\u5c04\u3001\u7624\u5185\u6ce8\u5c04\u7b49\u30022\uff09\u5c06mRNA\u75ab\u82d7\u8f6c\u5165\u79bb\u4f53\u7684DC\u7ec6\u80de\uff0c\u518d\u56de\u8f93\u7ed9\u75c5\u4eba\uff08ex vivo<\/em> DC mRNA vaccine\uff0c\u7c7b\u4f3c\u4e8eCAR-T\u7684\u6d41\u7a0b\uff09\uff0c\u9014\u5f84\u4ea6\u5305\u62ec\u6dcb\u5df4\u7ed3\u5185\u6ce8\u5c04\u3001\u9759\u8109\u6ce8\u5c04\u3001\u7624\u5185\u6ce8\u5c04\u7b49\u3002<\/span><\/p>\n<\/li>\n<\/ul>\n


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

          \u76f4\u63a5\u6ce8\u5c04\u3002<\/span><\/strong>\u76f4\u63a5\u6ce8\u5c04\u7684\u4f18\u52bf\u662f\u6210\u672c\u4f4e\uff0c\u6613\u64cd\u4f5c\uff0c\u5468\u671f\u77ed\u3002\u5fb7\u56fdCureVac\u516c\u53f8\u5f00\u53d1\u7684\u6297\u80bf\u7624RNA\u75ab\u82d7\u7ed3\u5408\u4e86\u9c7c\u7cbe\u86cb\u767d\u4fee\u9970\uff0c\u9776\u5411\u591a\u4e2a\u80bf\u7624\u6297\u539f\uff0c\u5e76\u4ee5\u81ea\u8eab\u4e3a\u4f50\u5242\uff0c\u5728\u4e34\u5e8a\u524d\u548c\u4e34\u5e8a\u8bd5\u9a8c\u4e2d\u5747\u53d6\u5f97\u4e86\u826f\u597d\u7684\u7597\u6548\u3002\u7f8e\u56fdModerna\u516c\u53f8\u4e5f\u662fmRNA\u80bf\u7624\u75ab\u82d7\u9886\u57df\u7684\u4e3b\u8981\u53c2\u4e0e\u8005\u4e4b\u4e00\uff0c\u6210\u7acb8\u5e74\u6765\u5df2\u878d\u8d44\u8d85\u8fc720\u4ebf\u7f8e\u91d1\uff0c\u4f30\u503c75\u4ebf\u7f8e\u91d1\uff0cModerna\u7684mRNA\u75ab\u82d7\u4e3b\u8981\u4f7f\u7528LNPs\u8f7d\u4f53\u3002\u53e6\u5916\u503c\u5f97\u4e00\u63d0\u7684\u662f\u6dcb\u5df4\u7ed3\u5185\u6ce8\u5c04\u7684mRNA\u75ab\u82d7\uff0c\u53ef\u4ee5\u63d0\u9ad8mRNA\u88abDC\u7ec6\u80de\u6444\u53d6\u8fdb\u800c\u6fc0\u6d3bT\u7ec6\u80de\u7684\u6548\u7387\u3002\u5fb7\u56fdBioNTech\u516c\u53f8\u5f00\u53d1\u4e86\u7f16\u7801NY-ESO-1\uff08\u4e00\u79cdTAA\uff09\u7684mRNA\u75ab\u82d7RBL001\/RBL002\uff0c\u5df2\u5b8c\u6210\u6dcb\u5df4\u7ed3\u5185\u6ce8\u5c04\u6cbb\u7597\u9ed1\u8272\u7d20\u7624\u7684I\u671f\u4e34\u5e8a\uff08NCT01684241\uff09\uff0c\u5b89\u5168\u6027\u826f\u597d\u3002\u8be5\u516c\u53f8\u57fa\u4e8e\u5176IVAC\u00ae-mutanome\u6280\u672f\u5e73\u53f0\u5f00\u53d1\u7684\u4e2a\u4f53\u5316mRNA\u75ab\u82d7\u540c\u6837\u5728I\u671f\u4e34\u5e8a\u4e2d\u83b7\u5f97\u79ef\u6781\u6548\u679c\uff08NCT02035956\uff09\uff0c\u7814\u7a76\u6570\u636e\u53d1\u8868\u57282017\u5e747\u6708\u7684\u4e00\u7bc7Nature\u6587\u7ae0<\/span>[3]<\/span><\/strong>\u3002\u4f46\u9700\u8981\u6307\u51fa\u7684\u662f\uff0c\u6dcb\u5df4\u7ed3\u5185\u6ce8\u5c04\u9700\u8981\u8d85\u58f0\u8f85\u52a9\u5b9a\u4f4d\uff0c\u4e14\u9700\u591a\u6b21\u7ecf\u76ae\u63a5\u79cd\u4f7f\u5f97\u5b9e\u9645\u64cd\u4f5c\u53d8\u5f97\u590d\u6742\uff0c\u53ef\u884c\u6027\u964d\u4f4e\u3002<\/span><\/p>\n


          <\/p>\n

          mRNA\u8f6c\u5165\u79bb\u4f53DC\u7ec6\u80de\u3002<\/span><\/strong>mRNA\u8f6c\u5165\u79bb\u4f53DC\u7ec6\u80de\u7b56\u7565\u7684\u4f18\u52bf\u662f\u53ef\u4ee5\u66f4\u9ad8\u6548\u5730\u6d3b\u5316DC\u7ec6\u80de\uff0c\u8fd9\u4e2a\u6280\u672f\u4e5f\u53ef\u770b\u4f5c\u662f\u7ecfmRNA\u6d3b\u5316\u7684DC\u7ec6\u80de\u75ab\u82d7\uff08\u5df2\u6709\u4e00\u6b3eDC\u7ec6\u80de\u75ab\u82d7\u88abFDA\u6279\u51c6\uff0c\u5373Provenge (Sipuleucel-T)\uff0c\u4f46\u5e02\u573a\u5316\u63a8\u5e7f\u7b56\u7565\u9700\u6539\u5584\uff09\u3002Neo-antigen mRNA\u75ab\u82d7\u540c\u6837\u662f\u8be5\u65b9\u5411\u7684\u70ed\u70b9\uff0c\u4e2a\u4f53\u5316\u7684mRNA\u4ee5\u7535\u7a7f\u5b54\u6cd5\u6216\u8f6c\u67d3\u6cd5\u8f6c\u5165\u5206\u79bb\u7684\u75c5\u4eba\u81ea\u4f53DC\u7ec6\u80de\u3002\u76ee\u524d\u5f00\u53d1\u8fdb\u5c55\u6700\u5feb\u7684\u662f\u7f8e\u56fdArgos Therapeutics\u7684Rocapuldencel-T\uff0c\u5728II\u671f\u6cbb\u7597\u80be\u764c\u7684\u4e34\u5e8a\u8bd5\u9a8c\u4e2d\u4e0e\u8212\u5c3c\u66ff\u5c3c\u8054\u7528\u53d6\u5f97\u4e86\u79ef\u6781\u7684\u7597\u6548\uff08NCT00678119\uff09\uff0c\u4f46\u7b14\u8005\u8fdb\u4e00\u6b65\u67e5\u8be2\u53d1\u73b0\uff0c\u8be5\u516c\u53f8\u7684\u5176\u4ed6\u4e34\u5e8a\u8bd5\u9a8c\u57fa\u672c\u5904\u4e8e\u7ec8\u6b62\u6216\u64a4\u9500\u7684\u72b6\u6001\uff0c\u8be5\u516c\u53f8\u7684\u80a1\u4ef7\u5df2\u5728$1\u4ee5\u4e0b\uff0c\u76ee\u524d\u53ef\u80fd\u6709\u8f83\u4e25\u91cd\u7684\u8d22\u52a1\u95ee\u9898\u3002\u603b\u4f53\u800c\u8a00\uff0cmRNA\u8f6c\u5165\u79bb\u4f53DC\u7684\u7b56\u7565\u6210\u672c\u8f83\u9ad8\uff0c\u4e14\u8017\u65f6\u8f83\u957f\uff0c\u6280\u672f\u96be\u5ea6\u8f83\u5927\uff0c\u56e0\u6b64\u4e34\u5e8a\u5e94\u7528\u524d\u666f\u53ef\u80fd\u53d7\u9650\u3002 <\/span><\/p>\n

           <\/span><\/p>\n

          \u76ee\u524d\u6709\u591a\u5bb6\u5927\u578b\u5236\u836f\u4f01\u4e1a\u901a\u8fc7\u81ea\u4e3b\u5f00\u53d1\u6216\u5408\u4f5c\u7684\u65b9\u5f0f\u8fdb\u5165mRNA\u80bf\u7624\u75ab\u82d7\u9886\u57df\u3002\u4e0a\u6587\u63d0\u5230\u7684BioNTech\u4e0e\u7f57\u6c0f\u3001\u62dc\u8033\u3001\u8d5b\u8bfa\u83f2\u548c\u8f89\u745e\u6709\u7814\u53d1\u5408\u4f5c\u9879\u76ee\uff1bCureVac\u4e0eBI\u3001\u5f3a\u751f\u548c\u8d5b\u8bfa\u83f2\u6709\u5408\u4f5c\uff1bModerna\u4e0e\u963f\u65af\u5229\u5eb7\u3001\u9ed8\u6c99\u4e1c\u6709\u5408\u4f5c\uff0c\u7b49\u7b49\u3002<\/span><\/p>\n

          \u5de5\u4e1a\u754c\u5904\u4e8e\u4e34\u5e8a\u5f00\u53d1\u9636\u6bb5\u7684mRNA\u80bf\u7624\u75ab\u82d7\u6c47\u603b\u89c1\u88681<\/span>\"RNA\u836f\u7269-\u80bf\u7624\u514d\u75ab\u7684\u4e0b\u4e00\u4e2a\u98ce\u53e3\uff1f\"<\/p>\n


          <\/p>\n

          2.3 RNA\u9002\u914d\u4f53\uff08RNA Aptamer\uff09<\/span><\/strong><\/h2>\n

          \u6838\u9178\u9002\u914d\u4f53\uff08Aptamer\uff09\u662f\u4e00\u7c7b\u65b0\u578b\u8bc6\u522b\u5206\u5b50\uff0c\u5176\u4f5c\u7528\u672c\u8d28\u662f\u4e00\u6bb5\u5355\u94fe\u6838\u9178\uff08DNA\u6216RNA\uff09\u5206\u5b50\u6298\u53e0\u5f62\u6210\u7279\u5b9a\u4e09\u7ef4\u7ed3\u6784\u800c\u4e0e\u751f\u7269\u9776\u6807\u9ad8\u4eb2\u548c\u529b\u548c\u9ad8\u7279\u5f02\u6027\u7ed3\u5408\uff0c\u7c7b\u4f3c\u4e8e\u6297\u4f53\u7684\u4f5c\u7528\u6a21\u5f0f\u3002\u7531\u4e8e\u5176\u5206\u5b50\u91cf\u8f83\u5c0f\uff0c\u53ef\u5316\u5b66\u5408\u6210\u3001\u7a33\u5b9a\u6027\u597d\u3001\u6bd2\u526f\u4f5c\u7528\u5c0f\uff0c\u514d\u75ab\u539f\u6027\u5c0f\u7b49\u4f18\u70b9\uff0c\u6838\u9178\u9002\u914d\u4f53\u5728\u8bb8\u591a\u65b9\u9762\u4f53\u73b0\u4e86\u4f20\u7edf\u7684\u514d\u75ab\u5b66\u4e0e\u5316\u5b66\u5206\u5b50\u8bc6\u522b\u65e0\u53ef\u6bd4\u62df\u7684\u4f18\u52bf\uff0c\u5728\u57fa\u7840\u7814\u7a76\u548c\u5e94\u7528\u9886\u57df\u6709\u4e86\u5feb\u901f\u7684\u53d1\u5c55\u3002<\/span><\/p>\n

           <\/span><\/p>\n

          SELEX\u6280\u672f\uff08\u6307\u6570\u5bcc\u96c6\u7684\u914d\u57fa\u7cfb\u7edf\u8fdb\u5316\u6280\u672f\uff0cSystematic Evolution of Ligands by Exponential Enrichment\uff0cSELEX\uff09\u53ef\u7528\u4e8e\u7b5b\u9009\u7279\u5f02\u6027\u4e0e\u9776\u7269\u8d28\u9ad8\u5ea6\u4eb2\u548c\u7684\u6838\u9178\u9002\u914d\u4f53\u3002RNA\u9002\u914d\u4f53\u8fd8\u9700\u6ce8\u610f\u8c03\u6574\u9aa8\u67b6\u5e8f\u5217\u6216\u6838\u82f7\u9178\u7ec4\u6210\uff0c\u4ee5\u907f\u514d\u88abRNA\u9176\u964d\u89e3\u3002<\/span><\/p>\n

           <\/span><\/p>\n

          \u5728\u80bf\u7624\u514d\u75ab\u9886\u57df\uff0c\u4e0d\u540c\u7c7b\u578b\u7684RNA\u9002\u914d\u4f53\u6709\u4e0d\u540c\u7684\u4f5c\u7528\u673a\u7406\uff0c\u5982\u56fe5\u6240\u793a\uff0c\u4e3b\u8981\u53ef\u5206\u4e3a\u56db\u7c7b\uff1a<\/span><\/p>\n


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

            \n
          • \n

            \u62ee\u6297\u578b\u9002\u914d\u4f53\uff08Antagonisticaptamer\uff09\u3002\u7528\u4e8e\u6cbb\u7597\u76ee\u7684\u7684\u9002\u914d\u4f53\u5927\u591a\u4e3a\u62ee\u6297\u578b\uff0c\u76ee\u524d\u5904\u4e8e\u4e34\u5e8a\u9636\u6bb5\u7684\u9002\u914d\u4f53\u5747\u4e3a\u62ee\u6297\u578b\u9002\u914d\u4f53\u3002\u5728\u4e34\u5e8a\u524d\u7814\u7a76\u4e2d\uff0c\u62ee\u6297\u578b\u9002\u914d\u4f53\u80fd\u591f\u6709\u6548\u6291\u5236\u591a\u79cd\u514d\u75ab\u8d1f\u8c03\u63a7\u5206\u5b50\u7684\u529f\u80fd\uff0c\u5305\u62ecCTLA4\uff0cTIM3\uff0cIL10\uff0cLAG3\u7b49\u3002<\/span><\/p>\n


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

          • \n

            \u6fc0\u52a8\u578b\u9002\u914d\u4f53\uff08Agonistaptamer\uff09\u3002\u514d\u75ab\u6fc0\u52a8\u6027\u5206\u5b50\u7684\u6fc0\u52a8\u578b\u9002\u914d\u4f53\u5c1a\u5904\u4e8e\u4e34\u5e8a\u524d\u5f00\u53d1\u9636\u6bb5\uff0c\u9488\u5bf9\u5305\u62ec4-1BB\uff0cOX40\uff0cCD28\uff0cCD40\u7b49\u70ed\u95e8\u9776\u70b9\u3002<\/span><\/p>\n


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

          • \n

            \u53cc\u7279\u5f02\u6027\u9002\u914d\u4f53\uff08Bispecific aptamer\uff09\u3002\u5df2\u5f00\u53d1\u7684\u67094-1BB\/PSMA\uff0cVEGF\/4-1BB\uff0cMRP1\/CD28\u7b49\u3002<\/span><\/p>\n


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

          • \n

            \u5d4c\u5408\u578b\u9002\u914d\u4f53\uff08Chimericaptamer\uff09\u3002
            <\/span><\/p>\n<\/li>\n<\/ul>\n

            \"RNA\u836f\u7269-\u80bf\u7624\u514d\u75ab\u7684\u4e0b\u4e00\u4e2a\u98ce\u53e3\uff1f\"<\/p>\n

            \u25b2\u56fe5. \u514d\u75ab\u8c03\u8282\u578bRNA\u9002\u914d\u4f53\uff08\u56fe\u7247\u6765\u6e90\uff1a\u5f15\u75281\uff09<\/span><\/p>\n


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

            \u9002\u914d\u4f53\u9886\u57df\u4e3b\u8981\u4f01\u4e1a<\/span><\/strong><\/p>\n

            \u6700\u65e9\u83b7\u6279\u4e0a\u5e02\u7684RNA\u9002\u914d\u4f53\u662f\u4e00\u6b3e\u6cbb\u7597\u8001\u5e74\u6027\u9ec4\u6591\u53d8\u6027\uff08\u773c\u79d1\u75be\u75c5\uff09\u7684\u9776\u5411VEGF\u7684\u9002\u914d\u4f53Pegaptanib\uff08\u57f9\u52a0\u4ed6\u5c3c\uff0c\u5546\u54c1\u540dMacugen\uff09\uff0c\u7531NeXstar Pharmaceuticals\u5f00\u53d1\uff08\u5df2\u88abGilead\u6536\u8d2d\uff09\uff0c\u4e8e2004\u5e74\u83b7\u5f97\u7f8e\u56fdFDA\u6279\u51c6\u3002\u76ee\u524d\u4e34\u5e8a\u8bd5\u9a8c\u4e2d\u8fd8\u6709\u591a\u79cd\u9488\u5bf9\u773c\u79d1\u75be\u75c5\u7684\u9002\u914d\u4f53\uff0c\u8fd9\u91cc\u4e0d\u505a\u8fc7\u591a\u4ecb\u7ecd\u3002<\/span><\/p>\n

             <\/span><\/p>\n

            \u5fb7\u56fdNOXXON\u516c\u53f8\u6709\u4e24\u6b3e\u9002\u914d\u4f53\u76ee\u524d\u5728\u4e34\u5e8a\u9636\u6bb5\u5f00\u53d1\u80bf\u7624\u514d\u75ab\u7597\u6cd5\uff0cNOX-A12\u548cNOX-E36\uff0c\u5206\u522b\u9776\u5411\u57fa\u8d28\u7ec6\u80de\u884d\u751f\u56e0\u5b501\uff08SCDF\uff09\u548cCCL2\u8fd9\u4e24\u79cd\u53d1\u6325\u514d\u75ab\u6291\u5236\u529f\u80fd\u7684\u8d8b\u5316\u56e0\u5b50\u3002NOX-A12\u4e0ePD-1\u5355\u6297Keytruda\u8054\u7528\u6cbb\u7597\u80f0\u817a\u764c\u7684I\/II\u671f\u4e34\u5e8a\u6b63\u5728\u8fdb\u884c\u4e2d\uff08NCT03168139\uff09\u3002<\/span><\/p>\n

             <\/span><\/p>\n

            \u4e00\u3001\u4ea7\u4e1a\u74f6\u9888&\u53d1\u5c55\u7b56\u7565<\/span><\/strong><\/h1>\n

            \u6280\u672f\u7684\u5feb\u901f\u9769\u65b0\u6781\u5927\u5730\u4fc3\u8fdb\u4e86RNA\u836f\u7269\u7684\u53d1\u5c55\uff0c\u4f46\u76ee\u524d\u4ecd\u6709\u4e00\u4e9b\u4ea7\u4e1a\u74f6\u9888\u4e9f\u5f85\u89e3\u51b3\u3002\u88682\u5f52\u7eb3\u4e86RNA\u836f\u7269\u76f8\u8f83\u4e8e\u6297\u4f53\u548c\u7ec6\u80de\u7597\u6cd5\u7684\u4e00\u4e9b\u4f18\u7f3a\u70b9\u3002<\/span><\/p>\n


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

            \u4ee5\u4e0b\u4e09\u4e2a\u65b9\u9762\u5bf9\u4e8e\u4f18\u5316RNA\u836f\u7269\u7597\u6548\u548c\u5b89\u5168\u6027\u81f3\u5173\u91cd\u8981\uff1a<\/span><\/p>\n


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

            \u7a33\u5b9a\u6027\u3002<\/span><\/strong>\u4ece\u8fdb\u5316\u7684\u89d2\u5ea6\u8bb2\uff0cRNA\u7684\u7a33\u5b9a\u6027\u662f\u53d7\u5230\u4e25\u683c\u8c03\u8282\u7684\uff0c\u4ece\u800c\u7ef4\u6301\u6b63\u5e38\u7684\u86cb\u767d\u8868\u8fbe\u548c\u7ec6\u80de\u529f\u80fd\u3002RNA\u7684\u7a33\u5b9a\u6027\u53ef\u4ee5\u901a\u8fc7\u4ee5\u4e0b\u7b56\u7565\u8c03\u8282\uff1aa\uff09\u5e8f\u5217\u4e2d\u52a0\u5165\u7279\u6b8a\u7684\uff0c\u4e0d\u88abRNA\u9176\u6c34\u89e3\u7684\u6838\u82f7\u9178\uff1bb\uff09\u8c03\u6574\u6216\u4eba\u5de5\u5d4c\u5165\u5404\u79cd\u529f\u80fd\u5143\u4ef6\uff0c\u59825\u2019\u7aef\u5e3d\u5b50\uff085\u2019 cap\uff09\uff0c3\u2019 \u975e\u7f16\u7801\u533a\uff083\u2019 UTR\uff09\u548cPoly-A\u5c3e\u5df4\u7b49\uff1bc\uff09\u5e8f\u5217\u5bc6\u7801\u5b50\u4f18\u5316\uff08codon optimization\uff09\u7b49\u3002<\/span><\/p>\n

             <\/span><\/p>\n

            \u9776\u5411\u9012\u9001\u3002<\/span><\/strong>\u7531\u4e8eRNA\u5e26\u8d1f\u7535\uff0c\u56e0\u6b64RNA\u836f\u7269\u5982\u4f55\u6709\u6548\u7a7f\u8d8a\u7ec6\u80de\u819c\uff08\u78f7\u8102\u53cc\u5206\u5b50\u5c42\u5e26\u8d1f\u7535\uff09\u4e5f\u6210\u4e3a\u4e86\u4e00\u4e2a\u95ee\u9898\u3002\u7ec6\u80de\u4e3b\u8981\u91c7\u53d6\u5185\u541e\u7684\u65b9\u5f0f\u6444\u53d6RNA\uff0c\u5982DC\u901a\u8fc7\u5de8\u80de\u996e\u4f5c\u7528\uff08Macropinocytosis\uff09\u3002\u53e6\u5916\uff0c\u5982\u524d\u6240\u8ff0\uff0c\u9009\u53d6\u5408\u9002\u7684\u8f7d\u4f53\u4ee5\u53ca\u7ed9\u836f\u9014\u5f84\u4e5f\u975e\u5e38\u91cd\u8981\u3002\u8102\u8d28\u4f53\u7eb3\u7c73\u7c92\uff08LNPs\uff09\u8f7d\u4f53\u3001\u76ae\u5185\u6ce8\u5c04\u7ed9\u836f\u7b49\u90fd\u53ef\u4ee5\u4fc3\u8fdb\u80bf\u7624\u75ab\u82d7\u7684\u7597\u6548\u3002<\/span><\/p>\n

             <\/span><\/p>\n

            \u526f\u4f5c\u7528\u3002<\/span><\/strong>\u4e3a\u4e86\u80fd\u6709\u6548\u51cf\u5c11\u6ce8\u5c04\u53cd\u5e94\u548c\u708e\u75c7\uff0c\u8981\u8003\u8651\u4f18\u5316RNA\u7684\u5e8f\u5217\/\u7ed3\u6784\u548c\u9012\u9001\u8f7d\u4f53\u3002\u76f8\u5e94\u7b56\u7565\u6709\uff1a\u4e25\u683c\u7b5b\u9009\u9ad8\u7eaf\u5ea6\u7684RNA\uff0c\u91c7\u7528\u5316\u5b66\u4fee\u9970\u7684\u6838\u82f7\u9178\uff0c\u4f7f\u7528LNP\u8f7d\u4f53\uff0c\u4f7f\u7528PEG\u4fee\u9970\u589e\u52a0\u836f\u7269\u534a\u8870\u671f\u7b49\u3002\u53e6\u5916\uff0c\u4e5f\u6709\u7814\u7a76\u4eba\u5458\u901a\u8fc7\u7b97\u6cd5\u9884\u6d4b\uff0c\u91c7\u7528\u591a\u91cdRNA\u6df7\u5408\u7269\u7b49\u624b\u6bb5\u51cf\u5c11\u8131\u9776\u6548\u5e94\uff08off-target effect\uff09\uff0c\u8fd9\u4e00\u70b9\u5728siRNA\u7b49RNA\u5e72\u6270\u9886\u57df\u5e94\u7528\u8f83\u591a\u3002<\/span><\/p>\n

             <\/span><\/p>\n

            \u8054\u5408\u7597\u6cd5<\/span><\/strong><\/p>\n

            \u524d\u6587\u63d0\u5230\uff0c\u591a\u9879\u5173\u4e8eRNA\u75ab\u82d7\u4e0ePD-1\u6297\u4f53\u8054\u7528\u7684\u4e34\u5e8a\u8bd5\u9a8c\u5df2\u5728\u8fdb\u884c\u4e2d\u3002\u4ece\u4f5c\u7528\u673a\u7406\u4e0a\u8bb2\uff0c\u8fd9\u79cd\u8054\u7528\u7b56\u7565\u662f\u8f83\u4e3a\u5408\u7406\u7684\uff0c\u5728PD-1\u5355\u6297\u62ee\u6297\u514d\u75ab\u68c0\u67e5\u70b9\u7684\u540c\u65f6\uff0c\u7531\u75ab\u82d7\u6fc0\u53d1\u7684\u56fa\u6709\u514d\u75ab\u548c\u83b7\u5f97\u6027\u514d\u75ab\u529f\u80fd\u5c06\u4ece\u4e0d\u540c\u7684\u65b9\u9762\u4fc3\u8fdb\u514d\u75ab\u7cfb\u7edf\u5bf9\u80bf\u7624\u7ec6\u80de\u7684\u6740\u4f24\uff0c\u4ece\u800c\u8fbe\u5230\u6cbb\u7597\u80bf\u7624\u7684\u76ee\u7684\u3002\u9700\u8981\u6ce8\u610f\u7684\u662f\uff0c\u8fd9\u79cd\u8054\u7528\u53ef\u80fd\u5f15\u53d1\u8f83\u4e3a\u5f3a\u70c8\u7684\u514d\u75ab\u53cd\u5e94\uff0c\u5bfc\u81f4\u526f\u4f5c\u7528\uff0c\u9700\u8981\u8c28\u614e\u63a2\u7d22\u5408\u9002\u7684\u5242\u91cf\u548c\u6cbb\u7597\u987a\u5e8f\u3002<\/span><\/p>\n

             <\/span><\/p>\n

            RNA\u836f\u7269\u4e0e\u653e\u5316\u7597\u7b49\u624b\u6bb5\u8054\u7528\u7684\u7b56\u7565\u5df2\u5728\u4e34\u5e8a\u524d\u6a21\u578b\u4e2d\u663e\u793a\u6548\u679c\uff0c\u9700\u8fdb\u4e00\u6b65\u5728\u4e34\u5e8a\u8bd5\u9a8c\u4e2d\u786e\u8ba4\u3002<\/span><\/p>\n


            <\/p>\n

            \u53c2\u8003\u6587\u732e<\/span><\/strong><\/p>\n

            1. Pastor F, Berraondo P, Etxeberria I, et al. An RNA toolbox for cancer immunotherapy[J]. Nature Reviews Drug Discovery, 2018, 17(10): 751.<\/span><\/p>\n

            2. Pardi N, Hogan M J, Porter F W, et al. mRNA vaccines\u2014a new era in vaccinology[J]. Nature Reviews Drug Discovery, 2018, 17(4): 261.<\/span><\/p>\n

            3. Sahin U, Derhovanessian E, Miller M, et al. Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer[J]. Nature, 2017, 547(7662): 222.<\/span><\/p>\n

            4. Burnett J C, Rossi J J. RNA-based therapeutics: current progress and future prospects[J]. Chemistry & biology, 2012, 19(1): 60-71.<\/span><\/p>\n

            5. Cross R. Can mRNA disrupt the drug industry?[J]. Chemical & Engineering News, 2018, 96(35): 34-40.<\/span><\/p>\n

            6.  RNA\u65b0\u836f\u7684\u6625\u5929\u6765\u4e34\u4e86\u5417\uff1f<\/span><\/p>\n

            7. RNA\u836f\u7269\uff1a\u4ece\u201dRNA\u4e16\u754c\u201c\u8d70\u5411\u4e34\u5e8a\u3002<\/span>http:\/\/blog.sina.com.cn\/s\/blog_8088f3700102wc7h.htm<\/span><\/p>\n<\/p><\/div>\n","protected":false},"excerpt":{"rendered":"

            \u4f5c\u8005 l Timbersaw \u7f16\u8f91 l \u7ec6\u80de\u623f\u95f4 \u8f6c\u8f7d\u81ea\uff1a \u4e00\u3001\u80cc\u666f 2018\u5e74\u8bfa\u8d1d\u5c14\u751f\u7406\u5b66\u548c\u533b\u5b66\u5956 […]<\/p>\n","protected":false},"author":1,"featured_media":61002,"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\/61001"}],"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=61001"}],"version-history":[{"count":1,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/posts\/61001\/revisions"}],"predecessor-version":[{"id":61009,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/posts\/61001\/revisions\/61009"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/media\/61002"}],"wp:attachment":[{"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/media?parent=61001"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/categories?post=61001"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/tags?post=61001"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}