Mutant purine nucleoside phosphorylase proteins and cellular delivery thereof
申请人:Ealick E. Steven
公开号:US20050214901A1
公开(公告)日:2005-09-29
A host cell stably transformed or transfected by a vector including a DNA sequence encoding for mutant purine nucleoside cleavage enzymes is provided. The transformed or transfected host cell can be used in combination with a purine substrate to treat tumour cells and/or virally infected cells. A nucleotide sequence encoding mutant
E. coli
derived purine nucleoside phosphorylase proteins which can be used in conjunction with an appropriate substrate to produce toxins which impair abnormal cell growth is also provided. A method is detailed for the delivery of toxin by generation withing target cells or by administration and delivery to the cells from without. Novel purine nucleosides are detailed that yield a cytotoxic purine upn enzymatic cleavage. A synthetic process for nucleosides is also detailed.
Gene Therapy of Cancer: Activation of Nucleoside Prodrugs with<i>E. coli</i>Purine Nucleoside Phosphorylase
作者:John A. Secrist、William B. Parker、Paula W. Allan、L. Lee Bennett、William R. Waud、Jackie W. Truss、Anita T. Fowler、John A. Montgomery、Steven E. Ealick、Alan H. Wells、G. Yancey Gillespie、V. K. Gadi、Eric J. Sorscher
DOI:10.1080/15257779908041562
日期:1999.4
During the last few years, many gene therapy strategies have been developed for various disease targets. The development of anticancer gene therapy strategies to selectively generate cytotoxic nucleoside or nucleotide analogs is an attractive goal. One such approach involves the delivery of herpes simplex virus thymidine kinase followed by the acyclic nucleoside analog ganciclovir. We have developed another gene therapy methodology for the treatment of cancer that has several significant attributes. Specifically, our approach involves the delivery off. coli purine nucleoside phosphorylase, followed by treatment with a relatively non-toxic nucleoside prodrug that is cleaved by the enzyme to a toxic compound. This presentation describes the concept, details our search for suitable prodrugs, and summarizes the current biological data.
PURINE NUCLEOSIDE PHOSPHORYLASE GENE THERAPY FOR HUMAN MALIGNANCY