Scientists have created a new method of
tackling tumors by combining three strands of microRNA. The gel-based
treatment was tested on laboratory mice, with the results showing it
to be hugely more effective than existing treatments such as
The study focused on the use of microRNA – more than 1,000 short strands of RNA that help fine-tune gene expression. When not working properly, strands of microRNA can cause diseases including cancers, making them an important area of study.
The big problem with using microRNA to treat cancer is the requirement to deliver the strands to tumors – something that's proved problematic in the past. The new research focused on tackling this issue, binding together multiple RNA strands and embedding them within a gel.
The researchers wound three strands of microRNA together to form a triple helix structure, which is much more stable than single or double strands. The triple helix, which contains two targeted RNA sequences and one for stability, was then combined with two MIT-developed polymers, known as dendrimer and dextran, to form a stable gel.
When brought into contact with a tumor, the gel-embedded microRNA is slowly absorbed into the cells, at which time enzymes break down the triple helix into its constituent components, allowing the two targeted microRNA strands to get to work.
The treatment is designed as a dual mode of attack. One of the microRNA strands mimics a naturally occurring microRNA called miR-205, which is routinely destroyed in cancer cells, while the other blocks a strand that's overactive in cancers, known as as miR-221.
To see how effective the new delivery method was, the researchers carried out tests on laboratory mice implanted with triple-negative breast tumors – a particularly difficult cancer to treat. The results were extremely positive, with the triple helix treatment resulting in a 90 percent shrink in tumor size, and a survival time of up to 75 days. Other treatments, including those that attack tumors with single or double strand microRNA delivery, resulted in death in less than seven days.
The breakthrough serves as a proof of concept for future study, with microRNA being perhaps the most promising candidate treatment for targeted cancer therapy. The researchers plan to continue their work, looking for microRNA combinations that could be effective at tackling other types of tumor, as well as using the technique to deliver other types of RNA and even DNA.
"We really want to identify the right targets and use this platform to deliver them in a very effective way," says MIT assistant professor Natalie Artzi.
The researchers published their findings in the journal Nature Materials.