Noguiez-Hellin P, Robert-Le Meur M, Laune S, Salzmann J L, Klatzmann D
Génopoïétic, Paris, France.
C R Acad Sci III. 1996 Jan;319(1):45-50.
This work was aimed at generating a novel system for gene transfer to tumor cell, combining the advantages of non-viral gene transfer methods with those of transfer by recombinant retroviruses. We replaced the env gene of an infectious Moloney murine leukemia provirus with the gene coding for the thymidine kinase of Herpes Simplex Virus 1 (HSV1-TK). The sole transfection of this construction allows the production of viral particles, and the encapsidation of a viral genome carrying transgene. We show that this gene is expressed at a level sufficient for conferring sensitivity to ganciclovir, a nucleoside analog that is metabolised in a toxic compound by HSV1-TK. We also show that the complementation of this recombinant defective provirus with a gene coding for a retroviral envelope, either expressed constitutively by the transduced cell, or by co-transfection, leads to the formation of infectious viral particles capable of transducing HSV1-TK into tumor cells.
这项工作旨在构建一种新型的肿瘤细胞基因转移系统，将非病毒基因转移方法的优势与重组逆转录病毒转移方法的优势相结合。我们用编码单纯疱疹病毒1型胸苷激酶（HSV1-TK）的基因替换了感染性莫洛尼鼠白血病前病毒的env基因。这种构建体的单独转染可产生病毒颗粒，并将携带转基因的病毒基因组包装起来。我们表明，该基因的表达水平足以赋予对更昔洛韦的敏感性，更昔洛韦是一种核苷类似物，可被HSV1-TK代谢为有毒化合物。我们还表明，用编码逆转录病毒包膜的基因对这种重组缺陷前病毒进行互补，该基因要么由转导细胞组成性表达，要么通过共转染，会导致形成能够将HSV1-TK转导到肿瘤细胞中的感染性病毒颗粒。
