New cancer therapy eliminates toxic delivery vehicles for mRNA
US researchers have conjugated RNA to a molecule of folate, the folate receptor is overexpressed on cancer cells but very low on normal cells, which is why they can target a tumour and avoid healthy cells…
US researchers have conjugated RNA to a molecule of folate, the folate receptor is overexpressed on cancer cells but very low on normal cells, which is why they can target a tumour and avoid healthy cells.
Unprotected RNAs can be degraded by two mechanisms — an exonuclease, or an endonuclease. By attaching the RNA to a folate, the researchers at Purdue University protected at least one end.
“Folate is generally pro-growth. That’s why cancer cells overexpress the receptor — they want more folate,” said Andrea Kasinski, a biology professor at Purdue who worked on the study. “We’re just hijacking that idea and saying, ‘Okay, you can have all the folate you want, but we’re going to conjugate it to a warhead that will hopefully knock out the cancer cell.'”
As cancer treatment moves toward targeted therapies, drug resistance is becoming a cause for concern. Cancer cells evolved rapidly, so if the agent used to treat it only targets one gene, that gene is likely to become resistant. MicroRNA often have many relevant targets, making it unlikely that the cancer cells will develop resistance.
This seems like a promising method for cancer treatment, but so far, it’s only been tested in mice. The same microRNA used in this study, miR-34a, made it to clinical trial and failed. Dr Kasinski’s team believes that one of the reasons it failed is because of the delivery vehicle, but there’s no way to be sure. Even if the RNA is somehow toxic, they’re delivering it at a much lower dose than what was used in the trial, and whatever isn’t taken up by the tumour is cleared from the organism very fast.
While this kind of therapy may not replace other methods for cancer treatment, it could help make others more effective. The microRNA in question is cytostatic, not cytotoxic — it won’t kill a cell, but it will stop it from growing. Given in combination with chemotherapy, it would break down the cells’ defences, making them more sensitive to the cytotoxic agent.
“I think everything we do scientifically, especially in a cancer lab, moves us closer to an effective cancer therapy. But there’s still more we need to do,” Dr Kasinski said. “Maybe there are other microRNAs that will be better.”