mechanism of action
What is an LNA-based drug?
LNA is a modification of RNA that contains an oxy-methylene bridge between the 2' and 4' carbons in the ribose ring. This bridge creates a bi-cyclic structure that locks the conformation of the ribose and is the key to the high stability and affinity of LNA to its complementary nucleotide sequence.
The most important features of LNA antisense oligonucleotides commonly observed across molecules of this class include:
- excellent specificity, providing optimal targeting
- increased affinity to targets providing improved potency in-vivo in many different tissues
- strong pharmacology upon systemic delivery without any need for complicated delivery vehicles
- scalable and cost-effective manufacturing
- well tolerated with predictable toxicology
- potential for oral delivery
To be an effective antisense drug, the oligonucleotide needs to have a number of characteristics that allow it to reach its RNA target in the cell intact, in sufficient quantity and with sufficient affinity to cause a pharmacologically meaningful response. Developing antisense oligonucleotides with such characteristics has proven a significant challenge for more than two decades. With the invention of LNA-based oligonucleotides, however, such antisense molecules have now become a reality.
Antisence MOA - Using antisense inhibition, high affinity binding of LNA-based oligonucleotides target mRNA, activating RNAse H and degrading mRNA, thereby reducing target protein levels
microRNA MOA - LNA-based oligonucleotide binds to the miRNA and prevents its activity inside the cell. This typically results in an increase in the miRNA's target protein expression
what are microRNAs?
The Santaris Pharma A/S LNA Drug Platform is the only technology with mRNA and microRNA targeted drugs in clinical trials, reinforcing the broad utility of the platform. The Company made medical history in 2008 when it advanced the world’s first microRNA drug, miravirsen, into clinical trials. microRNAs are a relatively newly discovered class of short RNAs that function naturally in cells to fine-tune the expression of genes. As a novel class of targets they have created significant excitement in the scientific community and drug industry where they are increasingly considered promising therapeutic intervention points. The unique combination of small size and very high affinity allows LNA-based drugs to potently and specifically inhibit mRNA and microRNA targets in many different tissues without the need for complex delivery vehicles.