Cellular Couriers Deliver CRISPR with a Flash of Light

CRISPR-Cas9 technology holds the promise of permanently repairing pathological mutations, yet getting the complex editing machinery inside cells remains a significant hurdle. Researchers have now devised a clever solution using extracellular vesicles (EVs)—nanosized membrane sacs that cells naturally use to communicate and transfer biological cargo like proteins and RNA.

The team developed a versatile, modular strategy to load these biological couriers with Cas9. They utilised the high-affinity binding between MS2 coat proteins and specific RNA sequences known as aptamers. By fusing the proteins to the EV structure and incorporating the aptamers into the CRISPR guide RNAs, they effectively locked the gene-editing tools inside the vesicles.

Crucially, the system includes a 'PhoCl' domain—a photocleavable linker that breaks when exposed to UV light. This allows the cargo to be released precisely when needed, ensuring the tool is not just delivered but made available for work. This method is not limited to standard gene cutting; the researchers demonstrated that the system is highly modular. The cargo can be readily exchanged for other variants, such as the transcriptional activator dCas9-VPR or the adenine base editor ABE8e. This robust approach offers a potential pathway for more effective genetic engineering and transcriptional regulation.