Cline J
Schweiz Med Wochenschr. 1986 Oct 25;116(43):1459-64.
Of the many techniques which have been used to introduce new genes into cells, four are of particular interest for gene therapy. Transfection has been most extensively studied and has been used to put new genes into mice and men. Homologous recombination offers the promise of curing certain mutations in situ, but is still largely unexplored. Injection of new genes into the nuclei of single cell embryos has had startling successes in animals, but there are many scientific and ethical issues to be resolved before such an approach can be considered for gene therapy. Retroviral vectors currently offer the most exciting prospect for introducing useful gene sequences into defective cells; however, safety issues and problems of low levels of gene expression are still to be resolved. It appears likely that the bone marrow will be the first target of gene therapy for genetic diseases. The marrow is accessible and contains proliferating stem cells which can transmit the new genes to progeny cells. The possibility of treating enzyme deficiency diseases and hemoglobinopathies by gene transfer is attractive. Experiments in two patients with thalassemia major indicate that it is feasible to introduce new genes into bone marrow cells of man and return the modified cells to hematopoietic sites.
在众多已用于将新基因导入细胞的技术中，有四种技术在基因治疗方面特别受关注。转染技术得到了最为广泛的研究，并已被用于将新基因导入小鼠和人体。同源重组有望原位修复某些突变，但在很大程度上仍未得到充分探索。将新基因注入单细胞胚胎的细胞核在动物实验中取得了惊人的成功，但在将这种方法用于基因治疗之前，还有许多科学和伦理问题有待解决。逆转录病毒载体目前为将有用的基因序列导入缺陷细胞提供了最令人兴奋的前景；然而，安全问题以及基因表达水平较低的问题仍有待解决。看起来骨髓很可能会成为基因治疗遗传性疾病的首个靶标。骨髓易于获取，且含有能够增殖的干细胞，这些干细胞可将新基因传递给子代细胞。通过基因转移治疗酶缺乏症和血红蛋白病的可能性很有吸引力。对两名重型地中海贫血患者进行的实验表明，将新基因导入人体骨髓细胞并将经过改造的细胞重新植入造血部位是可行的。
