small RNA Therapeutics

The biggest obstacle to creativity is breaking through the barrier of disbelief.

          —Rodney Mullen

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Clinical successes have established small RNAs as powerful therapeutics. We use structural and mechanistic insights into Argonaute to explore novel siRNA designs with improved efficacy and safety.

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RELEVANT PUBLICATIONS

• Organyl 5′‑Phosphates in siRNA Guide Strands: Structure–Function Relationships Governing Anchoring in Argonaute 2 and Metabolic Stability. bioRxiv 2026

• Structural basis for gene silencing by siRNAs in humans. bioRxiv, 2024

• Structure-Guided Control of siRNA Off-Target Effects. J Am Chem Soc. 2016 138(28):8667-9.

• Structural Analysis of Human Argonaute-2 Bound to a Modified siRNA Guide. J Am Chem Soc. 2016, 138(28):8694-7.

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