Gerrard A J, Hudson D L, Brownlee G G, Watt F M
Chemical Pathology Unit, Sir William Dunn School of Pathology, Oxford OX1, 3RE, UK.
Nat Genet. 1993 Feb;3(2):180-3. doi: 10.1038/ng0293-180.
Haemophilia B might be permanently cured by gene therapy--the introduction of a correct copy of the factor IX gene into the somatic cells of a patient. Here, we have introduced a recombinant human factor IX cDNA into primary human keratinocytes by means of a defective retroviral vector. In tissue culture, transduced keratinocytes were found to secrete biologically active factor IX and after transplantation of these cells into nude mice, human factor IX was detected in the bloodstream in small quantities for one week. This is the first demonstration of a therapeutic protein reaching the bloodstream from transduced primary keratinocytes. This may have implications for the treatment of haemophilia B and other disorders.
血友病B或许可通过基因疗法得到永久性治愈，即将凝血因子IX基因的正确拷贝导入患者的体细胞。在此，我们借助一种缺陷型逆转录病毒载体，将重组人凝血因子IX cDNA导入原代人角质形成细胞。在组织培养中，发现转导的角质形成细胞可分泌具有生物活性的凝血因子IX，并且将这些细胞移植到裸鼠体内后，在一周时间内可在血液中检测到少量的人凝血因子IX。这是首次证明治疗性蛋白质可从转导的原代角质形成细胞进入血液循环。这可能对血友病B及其他疾病的治疗具有重要意义。
