The lab develops programmable RNA systems that enable gene expression to be conditionally activated inside specific cell types, while remaining inactive in non-target cells. Rather than relying solely on delivery-based specificity, regulatory logic is encoded directly within the mRNA itself, allowing translation to occur only in cells exhibiting defined intracellular RNA signatures associated with cell identity or disease state.

This work is based on engineered group I self-splicing introns, RNA ribozymes that function as sequence-dependent regulatory switches. Using synthetic RNA engineering approaches, we design mRNA constructs in which ribozyme activity, and therefore protein expression, is activated only in the presence of specific endogenous RNA sequences. This creates a molecular self-authentication mechanism in which the target cell’s transcriptome directly controls mRNA activation.

By embedding sensing and logic at the RNA level, these self-activating mRNA systems address a central limitation of conventional mRNA technologies, off-target activity in non-desired cells. The platform is broadly applicable across biotechnology and medicine. In cancer, tumour-specific transcriptional states can be exploited to selectively activate therapeutic or cytotoxic mRNAs in malignant cells while sparing healthy tissue. More broadly, programmable RNA systems enable precise, cell-specific gene expression for applications including immunomodulation, regenerative medicine, and synthetic biology.