RARE Daily

Researchers Find Potential of RNA Silencing Therapy in Rare Mole Condition

June 19, 2024

Rare Daily Staff

Researchers at the Francis Crick Institute, UCL Great Ormond Street Institute for Child Health and Great Ormond Street Hospital for Children (GOSH) have designed a new genetic therapy that could alleviate debilitating giant moles in a rare skin condition.

In the future, the treatment could potentially be used to reverse the giant moles, and therefore reduce the risk of affected children and adults from developing cancer. It could also potentially reverse other more common types of at-risk moles as an alternative to surgery.

Small skin moles are common in the population, but in congenital melanocytic naevus syndrome (CMN), children are born with up to 80 percent of their body covered in big, painful or itchy moles, caused by genetic mutations acquired in the womb. These moles can sometimes develop into a severe type of cancer called melanoma.

In a study published in the Journal of Investigative Dermatology, the researchers silenced a gene called NRAS, which is mutated in the cells in these moles, in cells in a dish and in mice. NRAS belongs to a group of genes (RAS genes) that, when mutated, can cause moles, and can predispose to cancer.

The team used a genetic therapy called silencing RNA, which silences the mutated NRAS in mole skin cells. The therapy was delivered in special particles directly to mole cells.

They gave injections containing the therapy to mice with CMN, which silenced the NRAS gene after just 48 hours. They also tested it in cells and whole skin sections from children with CMN. Silencing the gene triggered the mole cells to self-destruct.

“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,” said Veronica Kinsler, principal group leader of the Mosaicism and Precision Medicine Laboratory at the Crick, professor of pediatric dermatology and dermatogenetics at GOSH/UCL, said. “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 people.”

The research was funded by the National Institute for Health and Care Research, Caring Matters Now Charity and Patient Support Group, LifeArc and the NIHR Great Ormond Street Hospital Biomedical Research Centre.

The researchers have been working closely with the Crick’s translation team to develop the technology towards patient benefit. This has included securing translational funds from LifeArc to carry out more research in mice to understand how the treatment works over a longer period.

Photo: Veronica Kinsler, principal group leader of the Mosaicism and Precision Medicine Laboratory at the Crick, and professor of pediatric dermatology and dermatogenetics at GOSH/UCL

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