Oligonucleotide Conjugates 

Aro’s solution to the challenge of effective targeting and delivery of oligonucleotides is to design and optimize Centyrins for cell surface receptor binding and internalization, thus dramatically increasing the efficiency of gene target modulation

Targeting and delivery of oligonucleotid

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 conjugate oligonucleotides and have established robust protocols for chemical conjugation of the oligonucleotide to the Centyrin.


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. 

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Centyrins enable effective targeting and productive delivery of both siRNA and antisense oligonucleotides


Centyrin-siRNA Conjugate Mechanism of Action
Centyrin-siRNA Conjugate Mechanism of Ac
Centyrin-siRNA Conjugates: Robust and Selective Gene Knockdown
Centyrin-siRNA Conjugates Achieve Robust and Selective Gene Knockdown.jpg

Early proof-of-concept studies in mice demonstrated that a muscle targeted Centyrin conjugated to siRNA for the housekeeping gene, AHA-1, can achieve up to 80% AHA-1 gene knockdown in muscle tissue after a single dose of conjugate.  There is limited or no effect in off-target tissues like the kidney and liver.  This effect can be titrated based upon the dose of conjugate given and has been proven to be durable in subsequent studies.

Mice dosed IV with PBS or 1, 3 or 10 mpk (siRNA) of Centyrin-AHA-1 conjugate

Tissues collected 2 weeks post single dose