基因转移治疗血友病B的动物试验和安全性探讨

本文报道了皮肤成纤维细胞基因治疗血友病Ｂ的新西兰大白兔试验及安全性检测。转有人凝血因子ＩＸｃＤＮＡ的兔皮肤成纤维细胞包埋于胶原基质中，然后进行不同方式的自体或同种异体移植，移植兔血浆中人ＩＸ因子蛋白有高水平的表达且持续稳定，腹腔移植有ＲＳＦ－ｐＣＭＶＩＸ转化细胞的兔血浆中人ＩＸ因子表达水平达１００ｎｇ／ｍｌ．持续５个月以上，腹腔移植有ＲＳＦ－ｐＣＭＶＩＸｌ转化细胞的兔血中人ＩＸ因子表达水平达２９５

RABBIT EXPERIMENTS AND RELATED SAFETY ASSESSMENT STUDY OF GENE TRANSFER THERAPY FOR HEMOPHILIA B

This paper reports the New Zealand rabbit experiment of gene transfer study for hemophilia B with skin fibroblasts. Rabbit skin fibroblasts transduced with retroviral vector containing human factor IX cDNA, were embedded in collagen and implanted into New Zealand rabbit autograftly or allograftly. Human FIX in plasma of rabbits intraperitoneally implanted with RSF-XLIX cells reached to 100ng/ml and has been lasting for over 5.5 months; Human FIX in rabbits intraperitoneally implanted with RSF-pCMVIX transformed cells reached to 295 ng/ml and has been lasting for 2 years;Human FIX in plasma of rabbits subcutaneously injected with cell collagen matrix of RSF-N2CMVIX reaced to 480ng/ml and has been lasting over 500 days. Western blot confirmed the 55KD protein expresed in rabbit plasma was indeed human FIX. Safty assesements showed that the approach of cell implantation was safe and no replication-competient virus, malignant transfomed cells & deterious effects were detected.