RNAi technology is evaluated not only as an extremely powerful instrument for functional genomic analyses but also as a potentially useful method to develop highly specific gene silencing therapeutic.

A research article to be published October 28 in the World Journal of Gastroenterology addresses the above issue. In this study, the researchers constructed vector-based expression systems in which sense and antisense strands of short VEGF sequences were transcribed into the hairpin structure under the control of the U6 promoter.

They demonstrate that siRNAs which targeted against VEGF efficiently reduced the transcript levels of VEGF mRNAs, ultimately resulting in a reduction in the levels of VEGF protein. Furthermore, this inhibition was shown to be highly selective and sequence-specific because control siRNAs had little inhibitory effects on expression and transcription of VEGF.

The researchers have further demonstrated that, in addition to the above-reported target sites in the VEGF genome, the specific 21-bp siRNAs targeting VEGF exerted efficient and specific inhibition on VEGF expression, suggesting a good method to inhibit the expression of VEGF.

Future studies will be centered on the evaluation of the anti-VEGF efficacy of RNAi vectors in valid animal models, as well as on the preclinical elucidation using the RNAi technology.

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We hope to learn how the gene affects outcome, said Inoue. It's possible that knowing which patients have the gene may be a prognostic factor for how they will respond to chemotherapy. The gene may also be a target for future drug development since high expression of Dmp1 significantly inhibited the growth of some lung cancer cells.

The study was conducted with the Center for Human Genomics at Wake Forest.

Lung cancer is the leading cause of cancer deaths in the world and accounts for more solid tumor deaths than any other cancers. More than 170,000 new cases are diagnosed each year in the United States and about 160,000 will eventually die of the disease, representing 30 percent of all cancer deaths.

Co-researchers were Ali Mallakin, Ph.D., the lead author, Takayuki Sugiyama, M.D., Pankaj Taneja, Ph.D., Lauren A. Matise, B.S., Donna P. Frazier, Ph.D., Mayur Choudhary, B.S., Gregory A. Hawkins, Ph.D., Ralph B. D'Agostino Jr., Ph.D., and Mark C. Willingham, M.D., all with Wake Forest.

Wake Forest University Baptist Medical Center is an academic health system comprised of North Carolina Baptist Hospital and Wake Forest University Health Sciences, which operates the university's School of Medicine. U.S. News & World Report ranks Wake Forest University School of Medicine 18th in primary care and 44th in research among the nation's medical schools. It ranks 35th in research funding by the National Institutes of Health. Almost 150 members of the medical school faculty are listed in Best Doctors in America.

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