Construction and expression of retroviruses encoding dual drug resistance genes in human umbilical cord blood CD34+ cells

A series of retro viral vectors encoding humanmdr1 gene alone as wetl as in combination with either humanmgmt gene or human mutantSer ³¹-dhfr gene are engineered. The resultant retroviruses are used to transduce human umbilical cord blood CD34⁺ cetls. It has been shown that expression of dual drug resistance genes in transduced cetls confers a broad range of resistance to both kinds of corresponding drugs. These data suggest a rationale for the use of such double chemoresistance gene constructs in anin vivo model in which transduced hematopoietic cetls will acquire multiple protection against the cytotoxic side effects of combination chemotherapy and may have future application in chemoprotection of normal tissues, thus killing tumor cetls more effectivety.