Using novel screens, we select Centyrins that have high affinity and specificity for a given cell surface receptor. We have designed a customized, high-throughput internalization screen to identify Centyrins that, once bound to a cell surface receptor, are subsequently internalized into the intracellular environment. We have identified specific amino acid sites on the Centyrin where we can site-specifically conjugate oligonucleotides and have established robust protocols for chemical conjugation.

 

Excellent stability properties enable Centyrins to avoid degradation pathways once inside the cell, and effectively deliver the oligonucleotide “payload” to the correct cellular compartment, with durable gene knockdown.