Ultrasound-powered nanomotors to deliver Cas9

CRISPR-Cas9 has been a revolution in genome editing, from bacteria to humans. However, the efficiency delivering Cas9 and the sgRNA is one of the limiting points in the process. Researchers used plasmid-base delivery systems, nano-vesicles or nano-particles to improve the efficiency delivering the CRISPR systems.

In this new article, “Active Intracellular Delivery of a Cas9/sgRNA Complex Using Ultrasound-Propelled Nanomotors” published in Angewandte Chemie the authors developed a transport vehicle attaching the Cas9 protein-sgRNA complex to a gold nanowire through sulfide bridges. Inside of the tumor cells, the linkages are broken by the glutathione which is highly produce in tumor cells. Then, Cas9–sgRNA is released and send to the nucleus to do its editing work.

The application of ultrasound accelerated the nanomotor carrying the Cas9–sgRNA complex across the cell membrane. The musical Cas9/sgRNA within the nanomotors display more than 80% knockout in the reporter GFPcompared to 30% knockout using static nanowires.

The authors displayed two clear advantages. i) an acoustic nanomotor that can serve as an active transport vehicle is part of relatively compact system; ii) the system is simple, requiring just a few and readily available components. Finally they concluded as “offers an attractive route to overcome physiological barriers for intracellular delivery of functional proteins and RNAs, thus indicating considerable promise for highly efficient therapeutic applications.”

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