Scientists improve delivery of cancer-fighting molecules

Aug 27, 2009
U-Iowa improves delivery of cancer-fighting molecules
A mouse tumor treated with an aptamer-siRNA combination (right) shows many dead areas (indicated by the asterisks), whereas an untreated tumor (left) is still largely intact. Delivering siRNA successfully to specific cells has been challenging. UI researchers modified siRNA so that it could be injected into the bloodstream and impact only targeted cells. Credit: University of Iowa

Small interfering RNA (siRNA), a type of genetic material, can block potentially harmful activity in cells, such as tumor cell growth. But delivering siRNA successfully to specific cells without adversely affecting other cells has been challenging.

University of Iowa researchers have modified siRNA so that it can be injected into the bloodstream and impact targeted cells while producing fewer side effects. The findings, which were based on animal models of prostate , also could make it easier to create large amounts of targeted therapeutic siRNAs for treating cancer and other diseases. The study results appeared online Aug. 23 in the journal .

"Our goal was to make siRNA deliverable through the bloodstream and make it more specific to the genes that are over expressed in cancer," said the study's senior author Paloma Giangrande, Ph.D., assistant professor of internal medicine and a member of Holden Comprehensive Cancer Center.

In previous research completed at Duke University, Giangrande's team showed that a compound called an aptamer can be combined with siRNA to target certain genes. When the combined molecule is directly injected into tumors in animal models, it triggers the processes that stop tumor growth. However, directly injecting the combination into tumors in humans is difficult.

In the new study, the researchers trimmed the size of a prostate cancer-specific aptamer and modified the siRNA to increase its activity. Upon injection into the bloodstream, the combination triggered tumor regression without affecting normal tissues.

Making the aptamer-siRNA combination smaller makes it easier to produce large amounts of it synthetically, Giangrande said.

The team also addressed the problem that large amounts of siRNA are needed since most of it gets excreted by the kidneys before having an effect. To keep siRNA in the body longer and thereby use less of it, the team modified it using a process called PEGlyation.

"If you want to use siRNA effectively for clinical use, especially for cancer treatment, you need to deliver it through an injection into the , reduce the amount of side effects and be able to improve its cost-effectiveness. Our findings may help make these things possible," Giangrande said.

Although the current study focused on prostate cancer, the findings could apply to other cancers and diseases. Giangrande said the next step is to test the optimized aptamer-siRNA compound in a larger .

Source: University of Iowa (news : web)

Explore further: How does enzymatic pretreatment affect the nanostructure and reaction space of lignocellulosic biomass?

add to favorites email to friend print save as pdf

Related Stories

Pack 'Em In -- Gold Nanoparticles Improve Gene Regulation

Feb 23, 2009

Investigators at Northwestern University have found that packing small interfering RNA (siRNA) molecules onto the surface of a gold nanoparticle can protect siRNAs from degradation and increase their ability to regulate genes ...

Team demos safety of RNA therapy

Sep 26, 2007

Researchers from MIT, Alnylam Pharmaceuticals and other institutions have demonstrated the safety of a promising type of genetic therapy that could lead to treatments for a wide range of diseases such as cancer.

Recommended for you

Quest to unravel mysteries of our gene network

20 hours ago

There are roughly 27,000 genes in the human body, all but a relative few of them connected through an intricate and complex network that plays a dominant role in shaping our physiological structure and functions.

EU court clears stem cell patenting

21 hours ago

A human egg used to produce stem cells but unable to develop into a viable embryo can be patented, the European Court of Justice ruled on Thursday.

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.