Evaluating a Targeted Cancer Therapy Approach Mediated by RNA trans-Splicing In Vitro and in a Xenograft Model for Epidermolysis Bullosa-Associated Skin Cancer

This research explores a method to selectively kill cancer cells using RNA trans-splicing, a process where parts of different RNA molecules are combined. The technique involves modifying a cancer target gene to express a 'suicide gene,' making tumor cells sensitive to a specific drug (ganciclovir), while leaving healthy cells unharmed. The study tests this approach on aggressive skin cancer associated with recessive dystrophic epidermolysis bullosa (RDEB), a rare genetic skin disease, using both lab experiments and a mouse model.

• 1
  RTM44, an RNA trans-splicing molecule, can effectively target the cancer gene Ct-SLCO1B3 in RDEB-SCC cells, leading to the expression of a fusion product at the mRNA and protein level.
• 2
  Systemic treatment with ganciclovir (GCV) in mice bearing RTM44-expressing cancer cells resulted in a significant reduction in tumor volume and weight compared to controls.
• 3
  The study demonstrates the applicability of RTM44-mediated targeting of the cancer gene Ct-SLCO1B3 in a different malignancy, expanding its potential use beyond colorectal cancer.