LNA Drug Platform and Drug Discovery Engine

The promise of RNA-targeted therapeutics

For two decades, RNA-targeted therapies have represented a promising new approach to drug development that offers compelling advantages over traditional small molecule and monoclonal antibody approaches.

Chief among the advantages of RNA-targeted medicines include the:

  • capability to be rationally designed on the basis of Watson-Crick base pairing rules thus enabling rapid and cost-effective identification of optimized drug leads
  • ability to access a host of disease-relevant targets that are undruggable by either small molecules or antibodies
  • predictability of pharmacokinetic/toxicology attributes which dramatically increases success rate in drug development and reduces candidate failures due to unanticipated toxicology and pharmacokinetic profiles
  • benefit of a reproducible, scalable and automatable drug manufacturing process, which improves Chemistry, Manufacturing and Control (CMC) efficiency and reduces infrastructure investment

Limitations with other approaches to developing RNA-targeted therapies

Despite significant investments and massive efforts in research and development of RNA medicines over the past two decades, there has been very limited progress in translating the appealing simplicity of RNA-targeted approaches into clinical benefits.

Typically, RNA-targeted therapies come in two varieties: (i) single-stranded approaches often referred to as "antisense"; and (ii) double-stranded approaches often referred to as "siRNA". A main limitation with antisense has been low-affinity for its RNA target, leading to insufficient potency and narrow therapeutic index in animals and humans. The chief problem with siRNA has been a relatively large molecule size, leading to poor cellular uptake and the need for complex and often toxic delivery vehicles.