Silencing genes to make moles self-destruct
Researchers have developed a promising new gene therapy that uses silencing RNA (siRNA) to induce self-destruction of congenital melanocytic naevus moles.
In a recently published study, researchers at the Francis Crick Institute, UCL Great Ormond Street Institute for Child Health and Great Ormond Street Hospital for Children (all London, UK) have seen early signs of success for a new targeted gene therapy designed to treat a rare skin condition called congenital melanocytic naevus syndrome (CMN) that causes debilitating giant moles.
CMN is a rare genetic disorder, most commonly caused by a mutation in the NRAS gene. It is a mosaic disorder, which occurs when one cell in the womb undergoes genetic mutation and, as the fetus develops, the cells derived from the mutated cell carry the CMN mutation, but other cells do not. Babies born with CMN develop fragile, itchy and painful moles that can cover up to 80% of their skin. Patients also carry an increased risk of developing melanoma.
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The research team designed a genetic therapy using siRNA to target the mutated NRAS gene in mole skin cells. They formulated lipid nanoparticles to protect the siRNA from degradation and facilitate its delivery into skin cells.
When injected into mice models of CMN, the therapy significantly reduced the expression of mutant NRAS within two days, without changing the expression of non-mutant equivalents in healthy cells.
To further test the treatment, the researchers administered the siRNA-containing nanoparticles to primary patient cells in vitro, as well as patient skin explants. The silencing effect of the siRNA triggered apoptosis in the CMN moles, causing them 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,” enthused Veronica Kinsler, senior Author of the study, “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.”
With the support of several charity sponsors, the research team is keen to progress the novel genetic therapy to benefit patients in the clinic.
