Scientists discovered that short strands of RNA known as microRNA help cells to fine-tune their gene expression. Disruption or loss of some microRNAs has been linked to cancer, raising the possibility of treating tumors by adjusting microRNA levels.
Developing such treatments requires delivering microRNA to tumors, which has proven difficult. However, researchers from MIT have now shown that by twisting RNA strands into a triple helix and embedding them in a biocompatible gel, they can not only deliver the strands efficiently but also use them to shrink aggressive tumors in mice.
Using this technique, the researchers dramatically improved cancer survival rates by simultaneously turning on a tumor-suppressing microRNA and de-activating one that causes cancer. They believe their approach could also be used for delivering other types of RNA, as well as DNA and other therapeutic molecules.
They wound three strands of microRNA together in a triple helix, creating a molecule that is much more stable than a single or double RNA strand. These triplexes then bind to dendrimer molecules, some of which form nanoparticles, and when dextran is added the injectable formulation gels on top of the solid tumor.
Once placed on the tumor, the gel slowly releases microRNA-dendrimer particles, which are absorbed into the tumor cells. After the particles enter the cells, enzymes cut each triple helix into three separate microRNA strands.
The researchers delivered two targeted microRNA sequences, plus a third strand whose only function is to keep the helix stable. One of the strands mimics the actions of a naturally occurring microRNA called miR-205, which is frequently silenced in cancer cells. The other blocks a microRNA called miR-221, which is often overactive in cancer cells.
The researchers tested the microRNA delivery platform in mice implanted with triple-negative breast tumors, which lack the three most common breast cancer markers: estrogen receptor, progesterone receptor, and Her2. Such tumors are usually very difficult to treat.
Treating these mice with microRNA delivered as a triple helix was far more effective than standard chemotherapy treatments, the researchers found. With the triple helix treatment, tumors shrank 90 percent and the mice survived for up to 75 days, compared with less than a week for other treatments (including single and double strands of the same microRNAs).
The microRNA combination used in this study appears to work by interfering with cancer cells’ ability to grow and to stick to other cells, the researchers found.
http://news.mit.edu/2015/microrna-shrink-tumor-cancer-treatment-1207
Edited
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