Using Proton Channels to Change pH and Help siRNA Escape from Cell Compartments

The Channel-PNA-siRNA (CPR) complex enhances gene regulation efficiency by reducing siRNA colocalization with lysosomes.

• CPR complex facilitates endosomal escape by inducing osmotic rupture of endosomes.
• The design uses the M2 proton channel to promote proton influx, aiding in siRNA delivery.
• Stable, non-covalent binding of siRNA is achieved through a peptide nucleic acid (PNA) linker.
• The CPR complex interrupts the endosomal pathway, potentially improving siRNA bioavailability.
• Dual-target gene knockdown is demonstrated by encapsulating multiple siRNAs within the liposome.

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