Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

Oligonucleotides - short DNA or RNA molecules - have great therapeutic application for a range of diseases. Yet, their potential has not been fully unleashed because of challenges linked to efficient delivery. Read more to find out about recent developments in oligonucleotide modifications, and the platforms that may be used to deliver them to target sites.

A pair of gloved hands arranging Eppendorf tubes on a rack in a laboratory setting. © Image by Belova59 from Pixabay

Oligonucleotide drugs have enormous potential to transform healthcare via the development of novel precision and/or personalized medicines for a plethora of unmet clinical needs. These include the neurodegeneration, rare diseases, cancers, viral infection, and disorders associated with ageing. Such oligonucleotide therapeutic modalities include gene silencing (e.g. by siRNA or gapmer oligonucleotides), modification of RNA processing (e.g. splice modulation using steric block oligonucleotides), gene activation, non-coding RNA inhibition, aptamers (which interact directly with a target protein), and genome editing using programmable nucleases (e.g. CRISPR-Cas9). Importantly, oligonucleotide-based therapeutics approaches are now reaching maturity, with ten drugs now approved by the US FDA. Many of these high-profile successes are limited to either local administration (e.g. to the eye or spinal cord) or delivery to liver after systemic injection. Indeed, the major hurdle to the development of oligonucleotide therapeutics is effective delivery of these molecules to their target tissues, cells, and sub-cellular sites of action. In the current issue of Nature Reviews Drug Discovery Dr Thomas Roberts and Professor Matthew Wood (from the Department of Paediatrics), together with Professor Robert Langer (MIT), discuss recent advances in oligonucleotide drugs delivery. This review provides an overview of oligonucleotide drug mechanisms of action and the plethora of chemical modifications which impart drug-like properties on these molecules. Established delivery strategies are discussed such as lipid nanoparticles and GalNAc bioconjugates (which both primarily target the liver), in addition to promising technologies being developed including exosomes, spherical nucleic acids, DNA nanostructures, and antibody conjugates.

Similar stories

Why we must expand newborn screening

Early diagnosis is of primary importance both to obtain the best effect of innovative medications and to accelerate their development, writes Professor Laurent Servais.

University spinout PepGen awarded major financing to target Duchenne muscular dystrophy

PepGen, a therapeutics company targeting severe neuromuscular diseases, including Duchenne muscular dystrophy (DMD), has closed a $45 million Series A funding round led by RA Capital Management with participation from Oxford Sciences Innovation (OSI), the company’s original seed investor.

Children’s pain ‘swept under the carpet for too long’ – Lancet Commission

The launch of Lancet Child and Adolescent Health Commission - the first ever to address paediatric pain - aims to raise the profile of children’s pain from early years to early adulthood.

Enriching Engagement (Round 2) awardees announced

The awardees for the second round of the University of Oxford’s Enriching Engagement funding scheme have now been announced, including a project from Paediatrics.

New design of ‘bike helmet’ style brain scanner used with children for first time

A new wearable ‘bike helmet’ style brain scanner, that allows natural movement during scanning, has been used in a study with young children for the first time. This marks an important step towards improving our understanding of brain development in childhood.

A call for blood and iron

Dr Sarah Atkinson’s research team investigates whether an iron export mutation in African populations can protect from anaemia, malaria and bacterial infections.