Structural exploration of locked nucleic acids (LNAs) for incorporation into anticancer oligonucleotides

Antisense oligonucleotides (AON) are short lengths of RNA or DNA molecules which are used to change gene expression to treat diseases like cancer and Parkinson’s disease. Like DNA, AONs are made up of chains of nucleotide units, but to make them useful as drugs, these nucleotides have to be structurally changed. Locked nucleic acids (LNAs) are a very useful type of altered nucleotide unit, since they are not broken down as quickly in the body, and attach strongly to the gene they are targeting. The problem with LNAs is that they are very difficult to make, so it is hard for chemists to make a lot of different changes to the structure of LNAs in order to find the best one to use in AONs.
The Britton research team recently discovered a new way to make LNAs very quickly and easily, in large amounts, from simple compounds. Using this new technology, we want to make a large number of structurally unique LNAs and, test them to find the best ones to use in AONs for the treatment of cancer.