Molecular recording is a novel way of tracking cellular signals in their biological context, alternative to microscopy and genomics. Our system, ProgRAM (Programmable RNA Access Memory), is based on RNA and thus a faster, transient and non-disruptive alternative. By employing the dCas13-ADAR system, it is possible to precisely record cellular events with a fluorescent protein "traffic light" readout, controlled by shifting the open reading frame resulting from sequential deamination of the start codon AUG to GUG. This allows for real-time visualization of cellular changes without invasive techniques like sequencing, following cell lysis. ProgRAM outperforms DNA-based systems by operating in the cytoplasm, enabling rapid responses and capturing transient signals that DNA systems miss. We extensively optimised our 5’ UTRs and protein sequences for high-yield multi-frame expression. As verified with academic experts, our system could have promising real-world applications for temporal monitoring in developmental biology, conditional therapeutics and gene therapy quality control.
The project was presented by Natalia Kuźmierkiewicz, Felipe Navarro and Matvii Lomonosov during the live stage presentation at iGEM 2024 Grand Jamboree in Paris. The recording was provided by the iGEM Foundation and can be also accessed on the iGEM Video Universe.
