New siRNA Therapy for Benign Lesions Could Reduce Risk for Future Cancer

Researchers have developed a novel genetic therapy for reversing the formation of giant moles in patients with congenital melanocytic naevus syndrome (CMN), thereby also reducing their risk for developing melanoma later on.

The therapy for this rare condition works by suppressing the NRAS gene (part of a group of RAS genes) that can cause moles and predispose to cancer when mutated, according to a news release about the research. Even though the researchers were working with mouse models for the study, they were optimistic that the therapy could work in human patients.

The authors of the study, published in the Journal of Investigative Dermatology, reported that using siRNA to target the NRASQ61K variant significantly reduced the expression of ARL6IP1. A single dose of siRNA triggered an apoptotic cascade in primary cells; this response not observed with MEK inhibitor treatment. The researchers delivered the siRNA in vivo using lipid nanoparticles in a humanized mouse model of melanocytic naevi. The result was a successful NRAS knockdown.

“CMN is physically and mentally challenging for children and adults living with this condition and for their families," Veronica Kinsler, principal group leader of the Mosaicism and Precision Medicine Laboratory at the Crick, a professor of pediatric dermatology and dermatogenetics at GOSH/UCL, and NIHR research professor, said in the news release. "These results are very exciting, as not only does the genetic therapy trigger self-destruction of the mole cells in the lab, but we have managed to deliver it into the skin in mice. These results suggest that the treatment in future could potentially reverse moles in people, however more testing will be needed before we can give it to patients."

Source: Bryant D, et al. Journal of Investigative Dermatology. Doi:10.1016/j.jid.2024.04.031.