New oligonucleotide analogues for therapeutic applications

Lead Research Organisation: University of Oxford
Department Name: Oxford Chemistry


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.


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Description We have developed oligonucleotide analogues with artificial backbones that can hybridise to complementary RNA sequences and are stable in cell culture. they have potential for use in therapeutic applications and this si the current focus of the project.
Exploitation Route First we have to carry out more work in cell culture. If the findings are still positive biologists can evaluate the oligonucleotide analogues in animal models and eventually if this is promising they could be considered as analogues to treat human diseases. We are endeavoring to disseminate our results by publication and at conferences so that the wider biological and biomedical community are aware of them. This is in addition to our own existing collaborations.
Sectors Healthcare,Pharmaceuticals and Medical Biotechnology

Description Award from the CRUK Oxford Centre Development Fund
Amount £12,500 (GBP)
Funding ID CRUKDF 0920 - YB TB 
Organisation Cancer Research UK 
Department Cancer Research UK (CRUK) Oxford Centre
Sector Private
Country United Kingdom
Start 07/2020 
Title A new platform technology for antisense therpaeutics 
Description We have developed novel chemical methods to constructs heavily modified oligonucleotides that show promising biological properties. The technology is versatile, and we have shown that it can be applied to any sequence of nucleobases Initial data suggests that the technology can improve the cellular uptake of antisense oligonucleotides and reduce their toxicity The technology has the potential to be automated, increasing its potenial appeal to industrial partners and also improving the future adoption of the technology. 
Type Of Material Technology assay or reagent 
Year Produced 2021 
Provided To Others? No  
Impact This technology has not yet been published or made available to other but will be once the relevant IP is protected 
Description Exon skipping collaboration 
Organisation University of Oxford
Department Department of Physiology, Anatomy and Genetics
Country United Kingdom 
Sector Academic/University 
PI Contribution Antisense assays for the project have been carried out the the Wood laboratory. Ysobel Baker (PDRA) has been performing cell culture and exon-skipping assays with guidance from the Wood Group
Collaborator Contribution The Wood group provided consumables, cell lines, and laboratory space for the project, along with critical input into experimental design.
Impact tbc
Start Year 2019