Targeted therapy with microRNAs slows the growth of cancerous tumors
The therapy causes cancer cells to absorb a fragment of RNA that naturally blocks cell division.Researchers at Purdue University have developed a technology to treat cancer using microRNA. A modified version of the molecule that targets cancer cells stops or slows cell division and tumor growth.
The scientists used a delivery system for the therapy that targeted cancer cells with microRNA-34a inside. This is a short double-stranded ribonucleic acid chain - a chain of ribonucleic acids attached like lightning teeth to a sugar-phosphate chain. The two strands are irregularly fastened together. These non-coding RNA molecules are abundant in healthy cells, but in cancer cells, their numbers are dramatically reduced.
To ensure that the modified microRNA-34a gets into cancer cells, the researchers attached a double strand to a folate molecule. All cells have receptors on the surface that bind to folic acid and pull the vitamin into the cell, but cancer cells have several times more of them and are therefore more sensitive to therapy.
The tiny microRNA-34a and folic acid compound penetrates the dense tissue of tumors and binds to the folic acid receptor on the cell surface. It is then pulled inward into a small sac of the cell membrane. Once inside the cell, some of the microRNA-34a leaves the vesicle and slows cell division.
Natural RNA degrades quickly, so to improve the longevity of the therapy, the team stabilized microRNA-34a by adding several small clusters of atoms along the length of the chain. Experiments in mouse models show that the modified version persists in cells for at least 120 h after administration.
Preclinical tests in mice showed that tumors treated with the new therapy did not increase in size during the 21-day study. In the control group, they tripled in size during this time. In addition, the therapy suppressed the activity of at least three genes - MET, CD44 and AXL - that cause cancer and resistance to other treatments.
The researchers are preparing to conduct clinical trials of the microRNA therapy.