MIT scientists develop promising triple helix cancer treatment
Scientists have created a new method oftackling tumors by combining three strands of microRNA. The gel-basedtreatment was tested on laboratory mice, with the results showing itto be hugely more effective than existing treatments such aschemotherapy.
The study focused on the use ofmicroRNA – more than 1,000 short strands of RNA that help fine-tunegene expression. When not working properly, strands of microRNA cancause diseases including cancers, making them an important area ofstudy.
The big problem with using microRNA totreat cancer is the requirement to deliver the strands to tumors –something that's proved problematic in the past. The new researchfocused on tackling this issue, binding together multiple RNA strandsand embedding them within a gel.
The researchers wound three strands ofmicroRNA together to form a triple helix structure, which is muchmore stable than single or double strands. The triple helix, whichcontains two targeted RNA sequences and one for stability, was thencombined with two MIT-developed polymers, known as dendrimer anddextran, to form a stable gel.
When brought into contact with a tumor, thegel-embedded microRNA is slowly absorbed into the cells, at whichtime enzymes break down the triple helix into its constituentcomponents, allowing the two targeted microRNA strands to get towork.
The treatment is designed as a dualmode of attack. One of the microRNA strands mimics a naturallyoccurring microRNA called miR-205, which is routinely destroyed incancer cells, while the other blocks a strand that's overactive incancers, known as as miR-221.
To see how effective the new delivery method was, the researchers carried out tests on laboratory miceimplanted with triple-negative breast tumors – a particularlydifficult cancer to treat. The results were extremely positive, withthe triple helix treatment resulting in a 90 percent shrink in tumorsize, and a survival time of up to 75 days. Other treatments,including those that attack tumors with single or double strandmicroRNA delivery, resulted in death in less than seven days.
The breakthrough serves as a proof ofconcept for future study, with microRNA being perhaps the mostpromising candidate treatment for targeted cancer therapy. Theresearchers plan to continue their work, looking for microRNAcombinations that could be effective at tackling other types oftumor, as well as using the technique to deliver other types of RNAand even DNA.
"We really want to identify the righttargets and use this platform to deliver them in a very effectiveway," says MIT assistant professor Natalie Artzi.
The researchers published theirfindings in the journal Nature Materials.