Alnylam and Collaborators Publish Pre-Clinical Research in Proceedings of the National Academy of Sciences
News Feb 12, 2009
Alnylam Pharmaceuticals, Inc. has announced the publication of new research in the Proceedings of the National Academy of Sciences (PNAS) by Alnylam scientists and collaborators from the Lankenau Institute for Medical Research and the David H. Koch Institute for Integrative Cancer Research at the Massachusetts Institute of Technology (MIT).
These new findings demonstrate that RNAi silencing of the claudin-3 protein using lipidoid formulations of small interfering RNAs results in the suppression of ovarian tumor growth and metastases. Claudin-3 is a tight junction protein that is highly over-expressed in approximately 90% 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.
“I am excited by these new data as there is a very significant need for novel therapies to treat patients with ovarian cancer – a devastating disease that affects more than 20,000 women and results in more than 15,000 deaths each year in the U.S. alone,” said Janet Sawicki, Ph.D., Professor at the Lankenau Institute for Medical Research. “Advanced-stage ovarian cancer is extremely difficult to treat with today’s medicines, and these new data suggest that an RNAi therapeutic targeting claudin-3 may represent a novel treatment option in the future.”
“These data further illustrate the broad potential of RNAi therapeutics in medicine,” said Daniel Anderson, Ph.D., of the David H. Koch Institute for Integrative Cancer Research at MIT. “We are excited by the pre-clinical 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 published data showed 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. Specifically, data with lipidoid-formulated claudin-3-specific siRNAs showed:
• In an ovarian cancer cell xenograft model with intratumoral injection, a significant silencing of claudin-3, a reduction in cell proliferation and tumor growth, and a significant increase in the number of apoptotic cells;
• In an ovarian tumor-bearing transgenic mouse model with intraperitoneal dosing, an approximately 40% suppression of tumor growth rate, including tumor regression in some mice, compared to controls, and a significant reduction of malignant ascites (fluid in the abdominal cavity that contains cancer cells), where only 22% of mice treated with the claudin-3 siRNA developed ascites compared to 75% of control-treated animals; and,
• In a mouse ovarian surface epithelial cell model with intraperitoneal dosing, a survival rate of 50% for siRNA-treated mice compared to 0% survival in control-treated animals.
In addition to ovarian tumors, claudin-3 is 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.
Schizophrenics' Blood Contains RNA From More MicrobesNews
The blood of schizophrenia patients features genetic material from more types of microorganisms than that of people without the debilitating mental illness, research at Oregon State University has found. What’s not known is whether that’s a cause or effect of the severe, chronic condition that strikes about one person in 100.READ MORE
Faulty Gene Leads to Alcohol-Induced Heart FailureNews
A faulty gene interacts with alcohol to accelerate heart failure in susceptible patients, a study suggests. This dangerous interaction can occur even when only moderate amounts of alcohol have been consumed.READ MORE