New oligonucleotide analogues for therapeutic applications

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Therapeutic oligonucleotides (Th-ONs) are rapidly becoming highly important agents for hard to treat diseases. They target mRNA thereby changing protein expression. With four Th-ONs now in the clinic; Eteplirsen, Nusinersen, Mipomersen and Patisiran, the market is worth billions of dollars. Moreover, with ~150 Th-ONs currently in clinical trials for cancer and other diseases the field is set for rapid commercial growth. Chemical modifications are essential to make ThONs bind tightly to their RNA targets, to resist enzymatic degradation in vivo and improve uptake into cells. Further improvements in these areas are urgently needed to improve efficacy, reduce toxicity and lower costs. In a BBSRC-funded project we have designed an entirely new class of ThONs (LNA-triazole and LNA-amide) to address these problems and we now plan to evaluate them in biological assays. When this data has been obtained we will file additional patents and set up a new company to exploit the technology.