Provision of positive and negative selections in retroviral vectors containing the cytosine deaminase gene

A. L. Shiau, H. M. Yang, P. Wu, C. L. Wu

研究成果: Article同行評審

9 引文 斯高帕斯(Scopus)

摘要

The E. coli cytosine deaminase (CD) provides a negative selection system for suicide gene therapy as CD transfectants are eliminated following 5-fluorocytosine (5FC) treatment. Here we report a positive selection system for the CD gene using 5-fluorouracil (5FU) and cytosine in selection medium to screen for CD-positive transfectants. It is based on the relief of 5FU toxicity by uracil which is converted from cytosine via CD catalysis, as uracil competes with the toxic 5FU in subsequent pyrimidine metabolism. Hence, a retroviral vector containing the CD gene may provide both positive and negative selections after gene transfer. The CD transfectants selected with the positive selection system showed susceptibility to 5FC in subsequent negative selection in vitro and in vivo. Therefore, this dual selection system is useful not only for combination therapy with transgene and CD gene, but can also act to eliminate selectively transduced cells after the transgene has furnished its effects or upon undesired conditions if 5FC is applied for negative selection in vivo.

原文English
頁(從 - 到)1571-1574
頁數4
期刊Gene Therapy
5
發行號11
DOIs
出版狀態Published - 1998

All Science Journal Classification (ASJC) codes

  • 分子醫學
  • 分子生物學
  • 遺傳學

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