Scientists at Purdue University have developed a microRNA therapy designed to slow tumor growth. The technology takes advantage of the tendency of several cancer types to express an excess of surface receptors that bind folate (vitamin B9) and draw it into the cell interior. By attaching the microRNA strand to a folate molecule, the researchers could target it to cancer cells. This targeting specificity is advantageous in reducing the potential for side-effects elsewhere in the body, and in reducing the required dose to achieve a tangible anti-cancer effect. The researchers hope that the treatment will expand the therapeutic arsenal available to oncologists when they are treating cancer.
MicroRNAs (shortened to miRNAs) are another RNA-based therapeutic, but unlike their recently famous cousin, messenger RNA, they typically block or otherwise modulate protein expression instead of coding for a protein themselves. In this case, these researchers have created an anti-cancer miRNA therapy that interferes with a series of genes that are important in cancer growth and are even involved in treatment resistance in certain tumors.
However, this was a challenge, as typically miRNAs are not stable enough to last for long in the body. The researchers were able to stabilize the miRNA strand using chemical modifications such that it is now stable and active for at least 120 hours within the body. The miRNA in question is called microRNA-34a, and it is normally found in relatively high levels in healthy cells, but is typically present at much lower levels in cancer cells, which ties in with their uncontrolled proliferation and cell division.
Restoring levels of microRNA-34a in cancer cells can help to reduce their growth and division, providing a brake on tumor activity. The researchers were also clever about targeting the treatment to cancer cells. They exploited the tendency of some tumors to overexpress folate receptors by binding a folate molecule to the miRNA. Cancer cells will bring the folate inside the cell interior using small vesicles, but in this instance, the miRNA therapy is also smuggled into the cell inadvertently.
So far, in a mouse study, the therapy was stable and active for at least 120 hours and stopped the growth of tumors over the space of 21 days, in contrast with control mice who showed tumor growth over this period. “When we acquired the data, I was ecstatic. I am confident that this approach is better than the current standard of treatment and that there are patients who will benefit from this,” said Andrea Kasinski, a researcher involved in the study.
Via: Purdue University
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