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:
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.
The Locked Nucleic Acid (LNA) Drug Platform utilizing Santaris Pharma A/S proprietary LNA chemistry provides the key to delivering on the promise of RNA-targeted therapies today by overcoming the limitation of earlier antisense and siRNA technologies. Above all else, the dramatic 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.