Pharma Focus America

Novel MicroRNA Therapy Shows Great Potential in Delaying Cancer Tumor Progression

Researchers at Purdue University have devised an innovative cancer therapy that employs a unique approach to impede the growth of tumors. This method tricks cancer cells into absorbing a fragment of RNA, which naturally hampers their ability to divide. In a 21-day study, tumors treated with this therapy showed no increase in size, in stark contrast to untreated tumors that tripled in size during the same period. Cancer, which can initiate in various parts of the human body, is marked by the uncontrolled proliferation of cells that can resist signals to cease division, evade apoptosis, and even elude the immune system.

In experiments using mouse models, this therapy combines a delivery system tailored to target cancer cells with a specially modified variant of microRNA-34a. In addition to its ability to inhibit tumor growth, this targeted microRNA-34a significantly suppressed the activity of at least three genes (MET, CD44, and AXL) that are well-known for their roles in promoting cancer and conferring resistance to conventional cancer treatments, maintaining this effect for an extended duration of at least 120 hours.

MicroRNA-34a is a short, double-stranded ribonucleic acid (RNA) molecule that resembles the interlocking teeth of a zipper running along the sugar-phosphate chain. In healthy cells, microRNA-34a is abundant, but its levels are substantially reduced in many cancer cells. Although reintroducing microRNA-34a to cancer cells might seem straightforward, the research team faced several challenges in developing an effective therapy.

Natural RNA degrades rapidly, so the team enhanced its stability by incorporating small atomic clusters along the strand's length. Additionally, the fully modified microRNA-34a remains undetectable to the immune system, which would typically react to double-stranded RNA introduced into the body. To ensure that the modified microRNA-34a reaches cancer cells, the team attached the double strand to a folate molecule.

This minute compound, composed of microRNA-34a and folate, can infiltrate the dense tissue of tumors and attach itself to the folate receptor on the cell surface. Subsequently, it is taken inside the cell within a vesicle, a small cellular membrane pouch. Once inside the cell, a portion of the microRNA-34a can escape from the vesicle, effectively slowing down the process of cell division.

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