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Harnessing MiRNA Natural Gene Repressors For Anticancer Therapy

Date:
December 9, 2008
Source:
Journal of Clinical Investigation
Summary:
Researchers have developed a new approach to harness natural repressors of gene expression known as miRNAs to modulate the expression of genes for therapeutic purposes and used this approach to mediate effective anticancer therapy in mice.

Michel Sadelain and colleagues, at Memorial Sloan-Kettering Cancer Center, New York, have developed a new approach to modulate the expression of genes for therapeutic purposes, and used this to mediate effective anticancer therapy in mice.

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Their study is published online, Dec. 1, 2008, in the Journal of Clinical Investigation.

Small, noncoding RNA molecules known as miRNAs are powerful natural repressors of gene expression. In the study, the miRNA miR-181a was harnessed to segregate expression of genes in immune cells known as T cells at different stages of their development. miR-181a is highly expressed in developing T cells, in which it represses expression of many genes, and markedly downregulated in mature T cells.

Sadelain and colleagues engineered mouse bone marrow cells to express therapeutic genes only when miR-181a expression is downregulated. These cells were then transplanted into mice and allowed to develop into mature T cells. Expression of the genes (and therefore the proteins made from the genes) was not detected in developing T cells, i.e., when miR-181a was highly expressed, but was detected in mature T cells, i.e., when miR-181a was downregulated.

When the genes controlled by miR-181a were responsible for making proteins that target T cells to tumor cells expressing the protein hCD19, the mice that were transplanted with the engineered bone marrow cells were able to reject tumors expressing hCD19.

The authors therefore suggest that it might be possible to harness miRNA-regulated therapeutic gene expression in stem cell–based therapies, including cancer immunotherapy.


Story Source:

The above story is based on materials provided by Journal of Clinical Investigation. Note: Materials may be edited for content and length.


Journal Reference:

  1. Papapetrou et al. Harnessing endogenous miR-181a to segregate transgenic antigen receptor expression in developing versus post-thymic T cells in murine hematopoietic chimeras. Journal of Clinical Investigation, 2008; DOI: 10.1172/JCI37216

Cite This Page:

Journal of Clinical Investigation. "Harnessing MiRNA Natural Gene Repressors For Anticancer Therapy." ScienceDaily. ScienceDaily, 9 December 2008. <www.sciencedaily.com/releases/2008/12/081201200034.htm>.
Journal of Clinical Investigation. (2008, December 9). Harnessing MiRNA Natural Gene Repressors For Anticancer Therapy. ScienceDaily. Retrieved December 19, 2014 from www.sciencedaily.com/releases/2008/12/081201200034.htm
Journal of Clinical Investigation. "Harnessing MiRNA Natural Gene Repressors For Anticancer Therapy." ScienceDaily. www.sciencedaily.com/releases/2008/12/081201200034.htm (accessed December 19, 2014).

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