Exciting research at MIT could be a new way to combat cancer.

For decades experts have known that short strands of RNA called microRNA help cells fine-tune gene expression, and that the disruption or loss of some microRNAs has links to cancer.

This has raised the possibility of treating tumours by adjusting microRNA levels, and a new MIT study could just be the key.

Researchers have 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 tumours in mice.

The team used the technique to dramatically improve cancer survival rates by simultaneously turning on a tumour-suppressing microRNA and de-activating one that causes cancer.

Even further, the approach could also be used for delivering other types of RNA, as well as DNA and other therapeutic molecules.

“This is a platform that can deliver any gene of interest,” says MIT researcher Natalie Artzi.

“This work demonstrates the promise of local delivery in combating cancer. In particular, as relates to gene therapy, the triplex structure improves RNA stability, uptake, and transfection efficacy.”

Artzi says it is the latest sign of a shift toward more targeted and selective treatments for cancer.

“Cancer is perceived as a systemic disease that mandates systemic treatment. However, in some cases, solid tumours can benefit from a local therapy that may include gene therapy or chemotherapy,” she says.

The researchers took advantage of an existing material made from two polymers known as dextran and dendrimer, as a tissue glue.

They exploited the ability of dendrimer to form a self-assembled structure with the microRNAs of interest.

First, 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 tumour.

Once placed on the tumour, the gel slowly releases microRNA-dendrimer particles, which are absorbed into the tumour cells.

After the particles enter the cells, enzymes cut each triple helix into three separate microRNA strands.

MicroRNA alters gene expression by disrupting messenger RNA molecules, which carry DNA’s instructions to cells’ protein-building machinery.

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 tumours, which lack the three most common breast cancer markers: oestrogen receptor, progesterone receptor, and Her2.

Treating the mice with microRNA delivered as a triple helix was far more effective than standard chemotherapy treatments, the researchers found.

With the triple helix treatment, tumours shrank 90 per cent 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 researchers are now looking into using this technique for delivering other types of nucleic acids, including short interfering RNA for RNA interference and DNA for gene therapy.

“We really want to identify the right targets and use this platform to deliver them in a very effective way,” Artzi says.

More details are available in the full study, published here.