SCIENCE OF RNAi

Delivery Challenges

While certain chemical modifications are able to successfully overcome this problem, there remains a larger challenge. 

siRNA Delivery Challenges
The challenges of systemic siRNA delivery are well documented and include numerous biological barriers that limit siRNAs from reaching their “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
        

Specifically, negatively-charged natural or modified siRNAs are typically 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 a 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.