{"id":32926,"date":"2018-10-03T00:26:53","date_gmt":"2018-10-02T16:26:53","guid":{"rendered":"https:\/\/case.ntu.edu.tw\/blog\/?p=32926"},"modified":"2018-09-28T10:13:35","modified_gmt":"2018-09-28T02:13:35","slug":"%e8%a1%80%e5%8f%8b%e7%97%85%e5%9f%ba%e5%9b%a0%e6%b2%bb%e7%99%82%e4%b9%9f%e9%81%8b%e7%94%a8%e6%ad%a6%e4%bf%a0%e5%b0%8f%e8%aa%aa%e7%9a%84%e6%af%92%e6%94%bb%e6%af%92%ef%bc%9f","status":"publish","type":"post","link":"https:\/\/case.ntu.edu.tw\/blog\/?p=32926","title":{"rendered":"\u8840\u53cb\u75c5\u57fa\u56e0\u6cbb\u7642\u4e5f\u904b\u7528\u6b66\u4fe0\u5c0f\u8aaa\u7684\u4ee5\u6bd2\u653b\u6bd2\uff1f"},"content":{"rendered":"

\u25a0\u4e00\u822c\u8a8d\u77e5\u85e5\u7269\u53ef\u4ee5\u6cbb\u75c5\u4f46\u4e5f\u5177\u6709\u6bd2\u6027\uff0c\u4f7f\u7528\u4e0d\u7576\u6703\u7522\u751f\u526f\u4f5c\u7528\uff0c\u7136\u800c\u5c6c\u65bc\u975e\u85e5\u7269\u7684\u57fa\u56e0\u6cbb\u7642\uff0c\u96e3\u9053\u4e0d\u662f\u653e\u7f6e\u6b63\u78ba\u7684\u57fa\u56e0\u5c31\u80fd\u9054\u5230\u6cbb\u7642\u76ee\u7684\uff1f\u600e\u9ebc\u6a23\u4ee5\u6bd2\u653b\u6bd2\u8b93\u6211\u5011\u4f86\u4e00\u63a2\u7a76\u7adf\u3002<\/strong><\/span><\/p>\n

\"\"\u64b0\u6587\uff5c<\/strong>\u694a\u671d\u5091<\/strong><\/p>\n

\u25cf\u57fa\u56e0\u6cbb\u7642\u958b\u555f\u8840\u53cb\u75c5\u60a3\u8005\u7684\u5e0c\u671b\u4e4b\u7a97<\/span><\/strong><\/p>\n

\u8840\u53cb\u75c5 (hemophilia) \u662f\u4e00\u7a2e\u5931\u53bb\u6b63\u5e38\u51dd\u8840\u529f\u80fd\u7684\u907a\u50b3\u6027\u75be\u75c5\uff0c\u53ef\u5206\u70ba\u5169\u5927\u985e\uff0c\u4e00\u7a2e\u70ba A \u578b\u8840\u53cb\u75c5\u7f3a\u4e4f\u7b2c\u516b\u51dd\u8840\u56e0\u5b50\uff0c\u53e6\u4e00\u7a2e\u70ba B \u578b\u8840\u53cb\u75c5\u7f3a\u4e4f\u7b2c\u4e5d\u51dd\u8840\u56e0\u5b50\u3002\u7531\u65bc\u662f\u57fa\u56e0\u7570\u5e38\u9020\u6210\u7684\u907a\u50b3\u6027\u75be\u75c5\uff0c\u6240\u4ee5\u4e00\u76f4\u4ee5\u4f86\u6c92\u6709\u5b8c\u5168\u6839\u6cbb\u8840\u53cb\u75c5\u7684\u85e5\u7269\u6216\u7642\u6cd5\uff0c\u6cbb\u7642\u65b9\u5f0f\u5927\u591a\u662f\u85c9\u7531\u975c\u8108\u6ce8\u5c04\u7d66\u4e88\u7f3a\u4e4f\u7684\u51dd\u8840\u56e0\u5b50\u4f86\u9810\u9632\u51fa\u8840\u3002\u7d04 15-20% \u8f03\u56b4\u91cd\u7684\u60a3\u8005\uff0c\u5728\u6cbb\u7642\u904e\u7a0b\u4e2d\u9084\u6703\u56e0\u70ba\u9ad4\u5167\u7522\u751f\u6291\u5236\u9ad4 (\u4e2d\u548c\u6027\u6297\u9ad4)\uff0c\u62b5\u6d88\u51dd\u8840\u56e0\u5b50\u7684\u6cbb\u7642\u6548\u679c\uff0c\u4f7f\u5f97\u6cbb\u7642\u8b8a\u5f97\u66f4\u52a0\u56f0\u96e3\u3002<\/p>\n

\u4e0d\u904e\u597d\u6d88\u606f\u662f\u5728 2011 \u5e74\uff0c\u82f1\u570b\u502b\u6566\u5927\u5b78\u7684 Amit Nathwani \u6559\u6388\u6210\u529f\u7814\u7a76\u4e86 B \u578b\u8840\u53cb\u75c5\u7684\u57fa\u56e0\u6cbb\u7642\uff0c\u521d\u6b65\u89e3\u6c7a\u4e86\u9577\u4e45\u4ee5\u4f86\u57fa\u56e0\u6cbb\u7642\u70ba\u4eba\u8a6c\u75c5\uff0c\u57fa\u56e0\u8868\u73fe\u91cf\u4e0d\u4f73\u7684\u4e00\u5927\u554f\u984c\u3002\u5176\u5be6\u57fa\u56e0\u6cbb\u7642\u7684\u7406\u8ad6\u4e26\u4e0d\u56f0\u96e3\uff0c\u901a\u5e38\u662f\u5229\u7528\u75c5\u6bd2\u4f5c\u70ba\u8f09\u9ad4 (vector) \u651c\u5e36\u60a3\u8005\u6240\u7f3a\u9677\u7684\u57fa\u56e0\uff0c\u5c07\u6b63\u78ba\u7684\u57fa\u56e0\u9001\u5165\u76ee\u6a19\u7d30\u80de\u5f8c\uff0c\u7d30\u80de\u4fbf\u80fd\u88fd\u9020\u6b63\u5e38\u7684\u86cb\u767d\u8cea\uff0c\u9032\u800c\u9054\u5230\u6cbb\u7652\u7684\u76ee\u7684\u3002Amit Nathwani \u6559\u6388\u662f\u5229\u7528\u817a\u76f8\u95dc\u75c5\u6bd2 8 (adenovirus-associated virus 8, AAV8)\uff0c\u5c07\u57fa\u56e0\u5bc6\u78bc\u5b50\u6700\u4f73\u5316\u7684\u7b2c\u4e5d\u51dd\u8840\u56e0\u5b50\u9001\u5165\u809d\u81df\u7d30\u80de\u8868\u73fe\uff0c\u7576\u6642\u7684\u6548\u679c\u5df2\u53ef\u9054\u5230\u6e1b\u5c11 90% \u4ee5\u4e0a\u7b2c\u4e5d\u51dd\u8840\u56e0\u5b50\u7684\u4f7f\u7528\u91cf\u3002\u9019\u6a23\u7684\u7d50\u679c\u76f8\u7576\u4ee4\u4eba\u632f\u596e\uff0c\u5f8c\u7e8c\u8a31\u591a\u81e8\u5e8a\u8a66\u9a57\u4e5f\u61c9\u904b\u800c\u751f\u3002<\/p>\n

\u25cf\u4ee5\u6bd2\u653b\u6bd2\u7684\u57fa\u56e0\u6cbb\u7642\u5176\u5be6\u662f\u7a2e\u622a\u9577\u88dc\u77ed<\/span><\/strong><\/p>\n

\u53d7\u5230\u8840\u53cb\u75c5\u4e4b\u6bd2\u5bb3\u6240\u82e6\u7684\u60a3\u8005\uff0c\u8a72\u600e\u9ebc\u7528\u57fa\u56e0\u6cbb\u7642\u4ee5\u6bd2\u653b\u6bd2\uff1f\u4e00\u5207\u5fc5\u9808\u5f9e B \u578b\u8840\u53cb\u75c5\u57fa\u56e0\u6cbb\u7642\u7684\u81e8\u5e8a\u8a66\u9a57 SPK-9001 \u8aaa\u8d77\uff0c\u5176\u70ba\u4e00\u9805\u7b2c I\/II \u671f\u81e8\u5e8a\u7814\u7a76\u65bc 2017 \u5e74\u767c\u8868\u7d50\u679c\u3002\u7814\u7a76\u9664\u4e86\u4f7f\u7528\u7279\u88fd\u7684\u75c5\u6bd2 AAV Spark-100 \u4f86\u63d0\u9ad8\u611f\u67d3\u809d\u81df\u7d30\u80de\u4e4b\u6548\u7387\u5916\uff0c\u66f4\u7279\u5225\u4e4b\u8655\u5728\u65bc\u5176\u6240\u651c\u5e36\u7684\u300c\u4e0d\u662f\u6b63\u5e38\u300d\u4e4b\u7b2c\u4e5d\u51dd\u8840\u56e0\u5b50\u57fa\u56e0\u3002\u88ab\u9078\u4e2d\u7684\u57fa\u56e0\u662f\u57282009 \u5e74\u7531\u7fa9\u5927\u5229\u79d1\u5b78\u5bb6 Paolo Simioni\uff0c\u5f9e\u4e00\u540d 23 \u6b72\u7684\u8840\u6813\u6813\u585e\u60a3\u8005\u8eab\u4e0a\u627e\u5230\u7684\u300c\u7a81\u8b8a\u578b\u300d\u7b2c\u4e5d\u51dd\u8840\u56e0\u5b50\u57fa\u56e0\uff0c\u7a81\u8b8a\u8655\u662f\u5728\u7b2c 338 \u4f4d\u7f6e\u7684\u80fa\u57fa\u9178\uff0c\u5f9e\u7cbe\u80fa\u9178 (arginine, R) \u66ff\u4ee3\u70ba\u767d\u80fa\u9178 (leucine, L)\uff0c\u6b64\u7a81\u8b8a\u7b2c\u4e5d\u51dd\u8840\u56e0\u5b50\u57fa\u56e0\u7c21\u7a31\u70ba IX-R338L\uff0c\u56e0\u70ba\u662f\u767c\u73fe\u5718\u968a\u4f86\u81ea\u7fa9\u5927\u5229\u5e15\u591a\u74e6\u5927\u5b78 (University of Padua) \u4e5f\u5225\u540d\u70ba F9-Padua\u3002\u7531\u65bc\u7a81\u8b8a\u578b IX-R338L \u7684\u6d3b\u6027\u662f\u6b63\u5e38\u7b2c\u4e5d\u51dd\u8840\u56e0\u5b50\u7684 5 \u81f3 10 \u500d\uff0c\u56e0\u6b64\u5047\u5982\u6b63\u5e38\u4eba\u5e36\u6709\u6b64\u57fa\u56e0\u53cd\u800c\u6703\u5f15\u767c\u8840\u6813\u6813\u585e\u75be\u75c5\u3002\u7136\u800c\uff0c\u5c0d\u4e00\u822c\u4eba\u81f4\u75c5\u7684 IX-R338L \u57fa\u56e0\uff0c\u537b\u5728 SPK-9001 \u8a66\u9a57\u4e2d\u6210\u529f\u904b\u7528\u65bc\u6cbb\u7642 B \u578b\u8840\u53cb\u75c5\uff0c\u9019\u6a23\u7684\u6cbb\u7642\u60f3\u6cd5\u4e26\u975e\u4e0a\u5929\u6240\u958b\u7684\u73a9\u7b11\uff0c\u800c\u662f\u985e\u4f3c\u65bc\u622a\u9577\u88dc\u77ed\u7684\u89c0\u5ff5\u904b\u7528\u3002<\/p>\n

\u25cf\u5373\u5c07\u8fce\u63a5\u66d9\u5149\u7684\u8840\u53cb\u75c5\u6cbb\u7642<\/strong><\/span><\/p>\n

SPK-9001 \u8a66\u9a57\u7684\u60a3\u8005\u6536\u7d0d\u689d\u4ef6\u70ba\u7b2c\u4e5d\u51dd\u8840\u56e0\u5b50\u6d3b\u6027\u4e0d\u8db3\u6b63\u5e38\u503c 2%\uff0c\u96d6\u7136\u53ea\u6709\u5c0f\u898f\u6a21\u7684\u7528\u5728 10 \u540d B \u578b\u8840\u53cb\u75c5\u60a3\u8005\uff0c\u4f46\u5728\u50c5\u9032\u884c\u4e00\u6b21\u6027\u7684\u4f4e\u5291\u91cf\u57fa\u56e0\u6ce8\u5c04\u6cbb\u7642\uff0c\u5c31\u80fd\u6709\u8457\u512a\u7570\u7684\u81e8\u5e8a\u7d50\u679c\u3002\u5728\u6ce8\u5c04\u5f8c\u7684 4 \u5468\u4e4b\u5167\uff0c\u60a3\u8005\u5011\u7684\u51dd\u8840\u56e0\u5b50\u6d3b\u6027\u5c31\u958b\u59cb\u4e0a\u5347\uff0c\u5728 14 \u5468\u6642\u57fa\u672c\u7a69\u5b9a\u5728\u6cbb\u7642\u76ee\u6a19\u503c (\u6b63\u5e38\u4eba\u7684 20\u201340%)\u3002\u904e\u7a0b\u4e2d\u53ea\u6709\u5169\u540d\u60a3\u8005\u51fa\u73fe\u4e86\u77ed\u66ab\u7684\u809d\u529f\u80fd\u6307\u6a19\u8840\u6e05\u8f49\u80fa\u9176 (alanine aminotransferase, ALT) \u5347\u9ad8\uff0c\u5728\u63a5\u53d7\u985e\u56fa\u9187\u6cbb\u7642\u5f8c\u4e5f\u8fc5\u901f\u7372\u5f97\u7de9\u89e3\uff0c\u4e26\u7121\u56b4\u91cd\u7684\u6cbb\u7642\u4f75\u767c\u75c7\u51fa\u73fe\u3002\u57fa\u56e0\u6cbb\u7642\u5f8c\u8ffd\u8e64 1 \u5e74\u7684\u6b62\u8840\u6548\u679c\u76f8\u7576\u4ee4\u4eba\u9a5a\u8276\uff0c\u51fa\u8840\u983b\u7387\u5f9e 11.1\u6b21\/\u5e74\u964d\u70ba0.4\u6b21\/\u5e74\uff0c\u53ef\u4ee5\u7a31\u5f97\u4e0a\u5e7e\u4e4e\u6240\u6709\u60a3\u8005\u7684\u51fa\u8840\u4e8b\u4ef6\u70ba\u96f6\uff0c\u90e8\u5206\u539f\u672c\u70ba\u9810\u9632\u6027\u6cbb\u7642\u7684\u60a3\u8005\uff0c\u5728\u57fa\u56e0\u6cbb\u7642\u5f8c\u4e5f\u7121\u9700\u9810\u9632\u6027\u6cbb\u7642\uff0c\u7b2c\u4e5d\u51dd\u8840\u56e0\u5b50\u7684\u4f7f\u7528\u91cf\u66f4\u662f\u6e1b\u5c11\u4e86 99%\u3002<\/p>\n

\u5728 2018 \u5e74\u4e16\u754c\u8840\u53cb\u75c5\u806f\u76df (World Federation of Hemophilia, WFH) \u5927\u6703\u4e2d\uff0cSPK-9001 \u8a66\u9a57\u4e5f\u66f4\u65b0\u4e86\u8ffd\u8e64 2 \u5e74\u7684\u6578\u64da\uff0c\u6240\u6709\u60a3\u8005\u7684\u7b2c\u4e5d\u51dd\u8840\u56e0\u5b50\u4ecd\u7136\u7e7c\u7e8c\u7dad\u6301\u8868\u73fe\u91cf\u3002\u9019\u9805\u7814\u7a76\u6210\u529f\u5be6\u73fe\u4e86\u6301\u4e45\u3001\u5b89\u5168\u7684\u57fa\u56e0\u6cbb\u7642\uff0c\u8b93 B \u578b\u8840\u53cb\u75c5\u60a3\u8005\uff0c\u6709\u4e86\u5fb9\u5e95\u8131\u96e2\u88dc\u5145\u51dd\u8840\u56e0\u5b50\u5e38\u898f\u6cbb\u7642\u7684\u5e0c\u671b\u3002\u53e6\u4e00\u65b9\u9762\uff0c\u96d6\u7136 A \u578b\u8840\u53cb\u75c5\u7684\u57fa\u56e0\u6cbb\u7642\u767c\u5c55\u8f03\u6162\uff0c\u76ee\u524d\u4e5f\u9084\u6709\u6c92\u767c\u73fe\u9069\u7528\u7684\u9ad8\u6d3b\u6027\u7a81\u8b8a\u578b\u7b2c\u516b\u51dd\u8840\u56e0\u5b50\uff0c\u4e0d\u904e\u76f8\u95dc\u7684\u81e8\u5e8a\u8a66\u9a57\u4e5f\u662f\u767e\u82b1\u9f4a\u653e\uff0c\u6709\u4e9b\u7814\u7a76\u5982 BMN 270 \u8a66\u9a57\u4e5f\u6709\u4e0d\u932f\u7684\u6210\u679c\u3002<\/p>\n

\u76f8\u4fe1\u5728\u4e0d\u4e45\u7684\u5c07\u4f86\uff0c\u8840\u53cb\u75c5\u4e0d\u518d\u7121\u6cd5\u6839\u6cbb\uff0c\u5728\u773e\u591a\u7814\u7a76\u5b78\u8005\u7684\u52aa\u529b\u4e0b\uff0c\u57fa\u56e0\u7642\u6cd5\u5b9a\u6703\u653b\u514b\u6b64\u4e00\u9b54\u5492\uff0c\u8840\u53cb\u75c5\u60a3\u8005\u5373\u5c07\u8fce\u5411\u66d9\u5149\uff01<\/p>\n

 <\/p>\n

\u53c3\u8003\u8cc7\u6599<\/strong>\uff1a<\/strong><\/p>\n

    \n
  1. Basics About Hemophilia<\/a>. CDC. August 28, 2018.<\/li>\n
  2. Nathwani AC, et al. Adenovirus-associated virus vector-mediated gene transfer in hemophilia B<\/a>. N Engl J Med. 2011;365:2357-65. <\/li>\n
  3. Gardl\u00edk R, et al. Vectors and delivery systems in gene therapy<\/a>. Med Sci Monit. 2005;11:RA110-21. <\/li>\n
  4. George LA, et al. Hemophilia B Gene Therapy with a High-Specific-Activity Factor IX Variant.<\/a> N Engl J Med. 2017;377:2215-2227. <\/li>\n
  5. Simioni P, et al. X-linked thrombophilia with a mutant factor IX (factor IX Padua)<\/a>. N Engl J Med. 2009;361:1671-5. <\/li>\n
  6. Sullivan, et al. Gene therapy reduces ABR, AIR in hemophilia B.<\/a> World Federation of Hemophilia 2018.<\/li>\n
  7. Rangarajan S, et al. AAV5-Factor VIII Gene Transfer in Severe Hemophilia A. <\/a>N Engl J Med. 2017;377:2519-2530. <\/li>\n<\/ol>\n

     <\/p>\n

    \"\u52a0\u5165\u597d\u53cb\"<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"

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