New oligonucleotide analogues for therapeutic applications

治疗性寡核苷酸(Th-ONS)正迅速成为治疗难治性疾病的重要药物。它们以信使核糖核酸为靶标，从而改变蛋白质表达。目前有四种Th-On药物进入临床：Eteplirsen、Nusinesen、Mipmer sen和Patisiran，这个市场价值数十亿美元。此外，目前约有150种Th-ONS正在进行癌症和其他疾病的临床试验，该领域将迎来快速的商业增长。化学修饰对于使Ton与其RNA靶标紧密结合、抵抗体内的酶降解以及提高对细胞的摄取至关重要。迫切需要在这些领域进一步改进，以提高疗效、降低毒性和降低成本。在BBSRC资助的一个项目中，我们设计了一类全新的Ton(LNA-三氮唑和LNA-酰胺)来解决这些问题，现在我们计划在生物检测中对它们进行评估。在获得这些数据后，我们将申请更多专利，并成立一家新公司来开发这项技术。

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.