Nelson D L, Chang S M, Henkel-Tigges J, Wager-Smith K, Belmont J W, Caskey C T
Cold Spring Harb Symp Quant Biol. 1986;51 Pt 2:1065-71. doi: 10.1101/sqb.1986.051.01.124.
Effective retroviral vectors carrying the human HPRT and ADA genes have been described. Initial characterization of the retroviral gene transfer system using the HPRT vector allowed the delineation of several parameters important in viral titer, expression, and stability. Using the HPRT and ADA vectors, we have initiated experiments designed to insert these human genes into various tissues of the mouse and have demonstrated expression of both transduced genes in mouse bone marrow cells. Further work with these and other vector constructions is underway in the hope that this technique may allow safe and effective treatment of ADA and HPRT deficiencies, paving the way for treatments of other inborn errors of metabolism through somatic gene replacement therapy.
已描述了携带人类次黄嘌呤磷酸核糖转移酶(HPRT)和腺苷脱氨酶(ADA)基因的有效逆转录病毒载体。使用HPRT载体对逆转录病毒基因转移系统进行的初步表征,确定了几个在病毒滴度、表达和稳定性方面很重要的参数。利用HPRT和ADA载体,我们已开展实验,旨在将这些人类基因插入小鼠的各种组织,并已证明转导基因在小鼠骨髓细胞中均有表达。目前正在对这些载体构建物及其他载体构建物开展进一步研究,希望这项技术能够安全有效地治疗ADA和HPRT缺陷,为通过体细胞基因替代疗法治疗其他先天性代谢缺陷铺平道路。