Silencing RNA causes moles to self-destruct in rare condition

Melanoma or skin cancer

UK researchers have designed a new genetic therapy that could alleviate debilitating giant moles in a rare skin condition.

The treatment could be used to reverse moles, and therefore prevent cancer. It could also potentially reverse other types of at-risk moles as an alternative to surgery.

In congenital melanocytic naevus syndrome (CMN), children are born with up to 80% of their body covered in big, painful or itchy moles. These moles can develop into melanoma.

The researchers from the Francis Crick Institute, UCL Great Ormond Street Institute for Child Health and Great Ormond Street Hospital for Children (GOSH) blocked the gene 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 cancer.

The team used a genetic therapy called silencing RNA, which blocks the action of the mutated NRAS in mole skin cells. The therapy was delivered directly to mole cells.

In mice with CMN the therapy reduced the expression of 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.

Veronica Kinsler, Principal Group Leader of the Mosaicism and Precision Medicine Laboratory at the Crick, Professor of Paediatric Dermatology and Dermatogenetics at GOSH/UCL, and NIHR Research Professor, said: “CMN is physically and mentally challenging for children and adults living with this condition and for their families. 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. This suggests that the treatment could potentially reverse moles in people.”

Diana Spencer, Senior Digital Content Editor, DDW

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