Designing siRNAs for improving their therapeutic applications

Small interfering RNAs (siRNAs) have the potential to revolutionize medicine due to their potency, duration of effect, and ability to target previously “undruggable” disease genes. The clinical success of siRNAs is dependent on their efficient delivery to disease tissues. However, as of today, clinically efficient siRNAs are limited to treat liver related diseases only. Robust and safe siRNA delivery in tissues beyond the liver remains a challenge and represents currently unmet technological needs. Thus, developing platforms that enable efficient and safe siRNA delivery to tissues beyond liver is the next milestone for expanding the utility of RNAi technology.

One of the most promising approach is to modulate oligonucleotide delivery through direct chemical modification and conjugation. Full chemical stabilization, identification of optimal conjugates and optimization of siRNA structure and modification content are essential to enabling sustained and robust efficacy following a single administration.

https://www.oligotherapeutics.org

Dr. Annabelle Biscans (AstraZeneca)
Annabelle Biscans is an Associate Principal Scientist in the Oligonucleotide Chemistry team at AstraZeneca R&D, Sweden. She has a robust expertise in designing and developing novel chemical modalities to improve oligonucleotide therapeutic delivery. Before joining AstraZeneca, she was a postdoctoral associate at the RNA Therapeutics Institute, USA in Anastasia Khvorova’s lab, one of the pioneers in oligonucleotide therapeutics research. There, she made major contributions to the development of novel chemical platforms for enhancing the delivery and uptake of siRNA therapeutics. She was able to design and identify novel conjugated siRNAs that enable safe, sustainable and robust silencing in various extra-hepatic tissues including muscle, heart, and lung. This crucial discovery allows for the targeting of several new targets for therapeutic intervention and advance the oligonucleotide therapeutics field.