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:
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.