New Delivery System Opens the Door to Gene-Silencing Therapy

The next generation of medications, known as antisense oligonucleotides (ASOs), works by preventing the transmission of damaging genetic messages. ASOs can prevent signals that promote tumor growth and dissemination in cancer patients.

ASOs are not currently being used to treat cancer. Cancer cells must first receive them, but they are resistant to entry.

Developing a successful ASO delivery system is a significant task. Gatekeeper molecules are present in cancer cells and prevent the entry of undesirable substances. Despite numerous attempts, investigators have not had much luck getting ASOs past the gatekeepers.

According to a recent study by Osaka University researchers published in the journal Nucleic Acids Research, there is now a method for getting ASOs to where they are required inside cancer cells. The group created a novel substance called L687 that causes certain calcium-permeable channels on the surface of cancer cells to open. The cells are instructed to allow the entry of ASOs when calcium enters through the open channels.

We discovered that we could selectively activate the TRPC3/C6 calcium permeable channels1) with the activator L687. We then found that combination treatment with L687 and ASO promoted efficient uptake of ASO into cancer cells during laboratory tests and tumor cells inside the mouse. As a result, target gene activity was suppressed and ASO efficacy was enhanced.”

Hiroto Kohashi, Lead Author, Osaka University

ASOs have historically been administered into the spinal fluid or liver to treat terminal illnesses. The study conducted by the Osaka team suggests that L687 is a potent medication delivery method that could help other body regions benefit from ASO treatment.

We hope that the results of our research will lead to significant progress in the development and delivery of ASOs and similar gene-targeting drugs for treating cancer.”

Masahito Shimojo, Senior Author, Osaka University

According to the team, L687 may be a particularly useful method of treating lung or prostate cancers with ASO therapy. Numerous TRPC3/C6 calcium permeable channels1) are present in these tumors, and L687 has the ability to open them, possibly identifying new targets for these next-generation treatments.