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

A series of retroviral vectors encoding human mdr1 gene alone as well as in combination with either human mgmt gene or human mutant Ser(31)-dhfr gene are engineered. The resultant retroviruses are used to transduce human umbi lical cord blood CD34(+) cells. It has been shown that expression of dual d rug resistance genes in transduced cells confers a broad range of resistanc e to both kinds of corresponding drugs. These data suggest a rationale for the use of such double chemoresistance gene constructs in an in vivo model in which transduced hematopoietic cells will acquire multiple protection ag ainst the cytotoxic side effects of combination chemotherapy and may have f uture application in chemoprotection of normal tissues, thus killing tumor cells more effectively.