LNA drug platform

The promise of RNA-targeted therapeutics

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

Chief among the advantages of RNA-targeted medicines are:

  • capability to be rationally designed on the basis of Watson-Crick base pairing rules to enable rapid and cost-effective identification of optimized drug leads
  • ability to access a host of disease-relevant targets that are not accessible by either small molecules or antibodies
  • a significant measure of predictability of pharmacokinetic/toxicology attributes to reduce drug candidate failure rate and increase the success rate in drug development
  • benefit of a reproducible, scalable and automatable drug manufacturing process to improve Chemistry, Manufacturing and Control (CMC) efficiency and reduce infrastructure investment

Limitations with other approaches to developing RNA-targeted therapies

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 significant limitation of antisense has been low-affinity for its RNA target, leading to insufficient potency and narrow therapeutic index in animals and humans. The number one disadvantage with siRNA compounds has been their relatively large molecule size, leading to poor cellular uptake and the need for complex delivery vehicles that can sometimes be associated with toxicity.

The solution: Santaris Pharma A/S Locked Nucleic Acid (LNA) Drug Platform

The LNA Drug Platform utilizing Santaris Pharma A/S proprietary LNA chemistry and tissue targeting technology provides the key to delivering on the promise of RNA-targeted therapies today by overcoming the limitation of earlier antisense and siRNA technologies. The increase in affinity that the LNA chemistry brings to oligonucleotides means that LNA-based drugs can be made much shorter than previous antisense drugs based on other chemistries, while displaying unprecedented affinity for their RNA targets. In turn, this unique combination of small size and very high affinity, which is only achievable with LNA-based drugs, allows this new class of antisense drugs to potently and specifically inhibit RNA targets in many different tissues without the need for complex delivery vehicles. Furthermore, conjugations to tissue targeting molecules enables LNA drugs to substantially accumulate in the desired target tissue(s) thereby lowering the dose required to obtain pharmacology and significantly increase the therapeutic index (TI).