Yam P Y, Yee J K, Ito J I, Sniecinski I, Doroshow J H, Forman S J, Zaia J A
Department of Virology and Infectious Diseases, City of Hope National Medical Center, Duarte, CA 91010, USA.
Exp Hematol. 1998 Sep;26(10):962-8.
In this study we compared the transduction efficiency of conventional amphotropic MoMLV (LPONL[A]) with the MoMLV pseudotyped with that of VSV-G (LPONL[G]) in peripheral blood progenitor cells (PBPCs) from cancer patients and human immunodeficiency virus (HIV)-infected donors. The results showed that LPONL(A) and LPONL(G) infected the progenitor cells from these sources with equal efficiencies. The transgene neoR was detectable by polymerase chain reaction assay in colonies from 14-day colony-forming unit (CFU) assays and in those derived from long-term culture-initiating cell (LTC-ICs) assays. Although the overall levels of transduction efficiency were similar in cord blood and PBPCs from noninfected cancer donors (25-22%) when either LPONL(G) or LPONL(A) was used, they were significantly lower in HIV-1-infected donors compared with noninfected cancer donors when LPONL(G) was used (13 vs. 25%; p = 0.027), and when LPONL(A) was used (12 vs. 22%; p = 0.087). The clonogenic potentials of infected and noninfected CD34+ cells were similar; thus no toxicity could be attributed to the virus preparation. We conclude that PBPCs from HIV-1-infected individuals are transduced less efficiently than those from non-HIV-infected cancer donors. Nonetheless, PBPCs from HIV-infected persons serve as potential targets in gene therapy for acquired immune deficiency syndrome.
在本研究中，我们比较了传统嗜亲性莫洛尼鼠白血病病毒（LPONL[A]）与假型化有水泡性口炎病毒糖蛋白（VSV-G）的莫洛尼鼠白血病病毒（LPONL[G]）对癌症患者外周血祖细胞（PBPCs）以及人类免疫缺陷病毒（HIV）感染供者的转导效率。结果显示，LPONL(A)和LPONL(G)对这些来源的祖细胞具有相同的感染效率。通过聚合酶链反应检测，在14天集落形成单位（CFU）检测的集落以及长期培养起始细胞（LTC-ICs）检测所衍生的集落中可检测到转基因neoR。尽管使用LPONL(G)或LPONL(A)时，脐血和未感染癌症供者的PBPCs的总体转导效率水平相似（25%-22%），但使用LPONL(G)时，HIV-1感染供者的转导效率显著低于未感染癌症供者（13%对25%；p = 0.027），使用LPONL(A)时也是如此（12%对22%；p = 0.087）。感染和未感染的CD34+细胞的克隆形成潜力相似；因此，病毒制剂未显示出毒性。我们得出结论，HIV-1感染个体的PBPCs的转导效率低于未感染HIV的癌症供者。尽管如此，HIV感染个体的PBPCs可作为获得性免疫缺陷综合征基因治疗的潜在靶点。
