RNA Interference Can Suppress Ovarian Tumor Growth

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 represent a promising new approach to the treatment of ovarian cancer. 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.

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.

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.

Release Date: February 9, 2009
Source: Massachusetts Institute of Technology