RNA-LNP Therapeutics for Resistant Melanoma

Melanoma, a deadly form of skin cancer, often becomes resistant to current treatments, particularly immunotherapy. Although melanoma tumors contain many genetic mutations, only a few are responsible for driving the cancer, such as mutations in key genes like BRAF, PTEN, p53, and p16. While targeted therapies like BRAF inhibitors offer temporary benefits, resistance usually develops, and many of these mutations are considered “undruggable” because no treatments can directly fix them. This creates a major gap in treatment options for patients, especially those whose cancer no longer responds to standard therapies.

Our research aims to address this issue by developing a new approach using RNA-lipid nanoparticles (LNPs) to deliver targeted treatments directly to melanoma cells. RNA-LNPs are tiny particles that can carry RNA molecules, such as small RNA molecules or mRNA, to specific tumor cells. These particles can be customized to target the unique mutations in each patient’s melanoma, offering a personalized treatment option. Early experiments have shown that these RNA-LNPs can successfully deliver treatments to melanoma cells and kill them. We have found that combining RNA that targets genes like p53 and p16 is especially effective at killing melanoma cells.

To improve this approach, we are working on making the delivery system more precise, ensuring that the RNA-LNPs target the melanoma tumor and not healthy tissues like the liver. We are also exploring ways to use antibodies that target melanoma cells, making the treatment even more specific.

Our research has two main goals: First, to improve how RNA-LNPs are delivered to melanoma tumors. Second, to test if these treatments can help overcome resistance to existing immunotherapies or make these therapies more effective in treating melanoma. If successful, this new treatment could offer hope for patients whose melanoma is no longer responding to current options and could be adapted for other cancers as well.