While mRNA vaccines work without needing precise cell targeting, cancer therapies require highly selective activation in tumor cells to avoid harming healthy tissue. A new study published in Molecular Therapy describes a novel solution: the selective modified RNA translation system (SMRTS), which builds cell selectivity directly into the mRNA itself rather than relying only on delivery systems.
SMRTS uses two engineered mRNAs to create an internal on/off switch controlled by the cell’s molecular environment. In healthy cells, an RNA-cutting enzyme (Cas6) is produced and shuts down the therapeutic gene. In cancer cells, cancer-specific microRNAs silence Cas6, allowing the therapeutic gene to be expressed. This enables highly selective activation of treatment only within tumor cells.
In mouse models of breast and colon cancer, cancer-specific SMRTS variants showed dramatic improvements in tumor-targeted expression and major reductions in off-target effects. Therapeutically, the system significantly suppressed tumor growth, with near-complete inhibition when combined with mRNA-derived immunotherapies.
Overall, SMRTS represents a major advance in mRNA therapeutics, offering a flexible platform for precise, safer treatments. Beyond cancer, the approach could potentially be adapted for other diseases requiring cell-specific targeting, expanding the clinical potential of mRNA well beyond vaccines.
Credit: https://www.genengnews.com