Study: U.S. job market is putting more workers in positions with limited upside and leverage.
Small RNA molecules can effectively keep ovarian tumors from growing and spreading in mice, according to a team of researchers from MIT, the Lankenau Institute for Medical Research and Alnylam Pharmaceuticals.
The findings, reported in the Feb. 9 online edition of the Proceedings of the National Academy of Sciences (PNAS), represent a promising new approach to the treatment of ovarian cancer, a disease that affects more than 20,000 women and results in more than 15,000 deaths each year in the United States alone. The work may also hold potential for treating other types of cancer.
The researchers used a new approach known as RNA interference (RNAi). RNAi therapeutics target disease by potently silencing specific messenger RNAs (mRNAs), thereby preventing disease-causing proteins from being made.
The new results demonstrate that RNAi silencing of the claudin-3 protein using lipid-like formulations of small interfering RNAs (siRNAs, the molecules that mediate RNAi) results in the suppression of ovarian tumor growth and metastases. Claudin-3 is a protein that is highly over-expressed in approximately 90 percent of ovarian tumors. Previous in vitro studies have shown that the over-expression of claudin-3 promotes migration, invasion and increased survival of ovarian cancer cells.
"These data further illustrate the broad potential of RNAi therapeutics in medicine," said Daniel Anderson, research associate at the David H. Koch Institute for Integrative Cancer Research at MIT. "We are excited by the preclinical efficacy of these siRNA formulations, as demonstrated in multiple animal models of ovarian cancer, and I am optimistic that the delivery systems described here will provide new avenues for the treatment of cancer and other diseases."
The researchers found that lipidoid-mediated delivery of siRNAs targeting claudin-3 in ovarian tumor tissue resulted in the dramatic silencing of the gene and a substantial reduction in tumor growth and metastases as compared to controls in three different mouse tumor models.
"We are encouraged by the findings published today in PNAS, as they represent a promising therapeutic approach that could significantly slow the progression of disease in patients with advanced-stage ovarian cancer," said David Bumcrot, director of research at Alnylam.
Claudin-3 is also over-expressed in other tumor types, including breast and prostate, and therefore lipidoid-mediated delivery of siRNAs targeting this protein may also be effective in the treatment of other cancers.
"These findings offer new hope for a therapeutic treatment option for individuals with metastatic ovarian cancer and potentially other types of cancers that over-express CLDN3," said Janet Sawicki, professor at the Lankenau Institute and an author of the paper. " Our next step is to begin Phase I clinical trials to test for safety with hopes to bring this treatment to the patient in the next few years."
Lipidoids are a new class of lipid-based molecules that are used to form novel nanoparticle formulations for systemic delivery of RNAi therapeutics. A previous study by MIT and Alnylam scientists showed successful delivery of siRNAs encapsulated in lipidoid formulations when administered in multiple animal species including mice, rats and nonhuman primates. Together, these data demonstrated potent, specific and durable effects on gene expression in multiple tissues, including liver, lung and peritoneal macrophages.
First author of the PNAS paper is Yu-Huang of the Lankenau Institute in Wynnewood, Pa. Other MIT authors are Michael Goldberg, postdoctoral associate in the Koch Institute; Kevin Love, technical assistant in the Department of Chemical Engineering; and Institute Professor Robert Langer.
The research was funded by the National Institutes of Health, Alnylam Pharmaceuticals, the Wawa Corporate Charities Program and the Sandy Rollman Ovarian Cancer Foundation.
This story was adapted from a press release issued by Alnylam Pharmaceuticals.