Researchers have developed a new platform called the Cancer-Selective modRNA Translation System (cSMRTS), which allows mRNA therapies to work only in cancer cells while avoiding healthy tissue. The system uses a dual mRNA “on/off” circuit based on microRNA patterns. In healthy cells, a sensor mRNA blocks the treatment. In cancer cells, tumor-specific microRNAs disable the sensor, allowing therapeutic proteins such as p53, Pten, or Pip4K2c to be produced. This approach increased tumor-specific activity up to 141-fold and reduced expression in major organs by 403-fold compared with standard mRNA.
The team tested cSMRTS in breast and colon cancer models and combined it with “modRNabs,” mRNA that instructs the body to produce its own anti-CTLA-4 antibodies. In colon cancer models, the combination reduced tumor volume by 93%, while in breast cancer models the reduction was 72%. The mRNA-produced antibodies performed as effectively as commercial versions.
The treatment also boosted anti-tumor immunity by increasing CD8 T cells and natural killer cells and reducing suppressive immune cells. Delivered systemically using lipid nanoparticles, it showed minimal liver and kidney toxicity. The findings suggest mRNA technology could be used to create more precise and less toxic cancer therapies beyond vaccines.