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SCIENCE OF RNAi

Delivery Challenges

Unlike antibodies or small molecule drugs, RNA are not stable and cannot circulate normally in the bloodstream due to the fact that they are degraded by numerous blood and tissue nucleases. 

RNAi DELIVERY CHALLENGE

The challenges of systemic RNAi delivery are well documented and include numerous biological barriers that limit an RNAi therapeutic’s ability to reach its “target” safely and effectively.

Rapid urinary excretion Rapid enzymatic degradation in the serum and tissues Non-specific tissue distribution Challenges of cellular uptake and intracellular release upon reaching the target cell Potential toxicities such as immunogenicity and cytokine release caused by siRNAs and/or delivery vectors Challenges of endosomal escape to achieve release of siRNA into the cytoplasm for incorporation into

While certain chemical modifications are able to successfully overcome this problem, there remains a larger challenge.  Specifically, negatively-charged natural or modified siRNAs are unable to be internalized inside the cell to reach their target in the cell cytoplasm.  This limitation has created a major hurdle for companies currently working toward the advancement of systemic RNAi therapeutics – the sustained systemic delivery of siRNA to the target tissue.  Without the means to selectively and effectively achieve targeted tissue and intracellular delivery of siRNA molecules, it will be impossible to unlock the full therapeutic potential of this exciting new class of drugs.