期刊
CANCER GENE THERAPY
卷 18, 期 9, 页码 682-684出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/cgt.2011.33
关键词
anti-cancer gene therapy specificity; transcript stability; cell division; 3 '-untranslated region; DNA methyltransferase I; Topoisomerase II alpha
类别
资金
- Russian Federal Agency for Science and Innovation [02.522.11.2005]
- Russian Academy of Sciences
Efficiency and specificity are two key attributes of anti-cancer drugs including genetic therapeutic agents. We suggest a way to improve specificity of gene therapy drugs based on the ability of 3'-untranslated regions (UTR) of some mRNAs selectively stabilize transcripts only during cell division. The mRNAs of genes encoding DNA methyltransferase I (DNMT1) and topoisomerase II alpha (TOP2A) are among such transcripts. When inserted into genetic constructs designed to produce therapeutic protein in tumor cells, such 3'-UTR would lead to diminished effect of therapeutic protein on normal cells, which are characterized by low or absent proliferative activity. However, when included in gene expression cassette, these 3'-UTR might result in decreased transgene expression, thus, overweighting the advantage of increased specificity of expression. We showed that DNMT1 and to the lesser extent TOP2A 3'-UTR do not alter significantly therapeutic transgene expression level in tumor cells, thus, confirming the functionality of the proposed approach. Cancer Gene Therapy (2011) 18, 682-684; doi: 10.1038/cgt.2011.33; published online 1 July 2011
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