Aiming to target the root cause of disease

Oligonucleotide therapeutics

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What are oligonucleotide therapeutics?

Oligonucleotide therapeutics are precisely designed strands of DNA or RNA that help us target an underlying biological process that drives disease. They modify the production of proteins — which are often the root cause of disease — offering advanced therapies that can be tailored, efficient, and better aligned with patients’ needs.

Why are oligonucleotides important?

Oligonucleotide therapeutics are creating new ways to address disease by targeting biology earlier in the disease process. Unlike many traditional medicines that work by targeting proteins, oligonucleotides work one step before that, at the RNA level providing a new way to target the drivers of disease and creating opportunities for influencing disease processes with enhanced precision.

This approach also offers practical advantages. Recent scientific advances mean oligonucleotides can now be targeted within the body and can stay active for longer than many traditional therapeutic options, which may allow for less frequent dosing and more flexible treatment routines that fit around patients’ lives.

Our ambition is to continue advancing oligonucleotide science to expand the availability of precise, patient‑centred treatment options across complex diseases.

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Oligonucleotides give us the unprecedented ability to target biological pathways previously out of reach in cardiovascular, renal, and metabolic disease and to explore therapies that can address the unmet needs of patients.

Regina Fritsche-Danielson, Senior Vice President, Early Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D

Oligonucleotide approaches at AstraZeneca

To precisely target the RNA (ribonucleoic acid) that drives the biology of disease, we are advancing two complementary oligonucleotide approaches: antisense oligonucleotide (ASO) and small interfering RNA (siRNA) therapies.

Each approach offers unique strengths, enabling tailored strategies to address diverse patient needs across complex conditions.

Antisense oligonucleotide (ASO) therapeutics

Single‑stranded oligonucleotides that can bind directly to RNA, allowing specific messages to be blocked, corrected or redirected to influence how disease‑related proteins are made.

Small interfering RNA (siRNA) therapeutics

Double-stranded oligonucleotides that are designed to bind and break down specific mRNA to stop the production of disease-related proteins.

What is the difference between ASO and siRNA therapeutics?

Applications of oligonucleotide therapeutics

Oligonucleotide therapeutics are unlocking new possibilities for previously undruggable targets across disease areas including cardiac disease, renal disease and certain rare diseases.

Oligonucleotides in cardiac disease

We are advancing oligonucleotide medicines to address the genetic drivers of cardiomyopathies in more targeted and durable ways.

Oligonucleotides in renal disease

We are advancing oligonucleotides to address the molecular pathways that contribute to chronic kidney disease.

Oligonucleotides in rare diseases

We are exploring the potential of siRNA therapies to address rare conditions with high unmet need.

The future of oligonucleotides at AstraZeneca

Oligonucleotides, including ASOs and siRNAs, enable us to target disease-driving biology at the RNA level with sequence-specific precision. By combining this with delivery to the right tissues, we are building on our expertise to explore novel therapeutic approaches with the potential to improve outcomes for patients.

Seng. H. Cheng, Senior Vice President, Research and Product Development at Alexion, AstraZeneca Rare Disease

How oligonucleotide therapies enable tissue-targeted delivery

We are pioneering new targeting platform technologies to improve outcomes for patients living with chronic and rare diseases and meet the challenges of delivering oligonucleotide therapeutics precisely to the tissues and cell types where they’re needed most.

Delivering to the liver

We use N-acetylgalactosamine (GalNAc ), a targeting approach that guides oligonucleotide-based therapies to specific cells in the liver called hepatocytes.
By focusing delivery where it’s needed, this can help limit effects elsewhere in the body.

Delivering to organs once out of reach

Through internal innovation and external collaboration, we are developing advanced targeting strategies to direct siRNA to harder-to-reach organs, such as the heart, helping medicines act directly within affected tissues.

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Reaching the exact cells in organs where disease begins is the challenge that drives us. We are pioneering targeted delivery approaches to finally bring previously inaccessible tissues within reach of oligonucleotide medicines.

Shalini Andersson, Vice President, Nucleic Acid Therapeutics, BioPharmaceuticals R&D

Collaborations

Strategic collaborations are helping us push the boundaries of oligonucleotide research, from new medicinal chemistry capabilities to targeted delivery. By combining internal innovation with external expertise, we aim to advance meaningful progress in this rapidly evolving field.

Ionis

We have a partnership with Ionis Pharmaceuticals to discover and develop RNA-targeted medicines for patients who need them most.

RNA Therapeutics Institute

We are collaborating with the RNA Therapeutics Institute, an academic department at UMass Chan Medical School to optimise antisense oligonucleotides (ASOs).

EU-funded consortiums

We are working with academic and industrial partners across Europe on several projects on oligonucleotides and targeted delivery.

Technical University of Dresden

In collaboration with Prof. Dr. Peter Mirtschink we are exploring uptake and trafficking of oligonucleotide-lipid conjugates in cardiomyocytes.

Novo Nordisk A/S

We partnered with Dicerna, part of Novo Nordisk A/S, to develop candidate siRNAs using the proprietary GalXC™ RNA interference (RNAi) platform to silence gene expression.

Oligonucleotide FAQs

What are oligonucleotides used for?

When used as therapeutics, oligonucleotides modulate RNA and modify disease-driving protein production, enabling precise, targeted treatments across conditions that traditional medicines cannot typically reach.

What is the difference between siRNA and mRNA?

siRNA breaks down mRNA to reduce the production of specific proteins, while therapeutic mRNA delivers genetic instructions to increase the levels of certain proteins.

What is the difference between oligonucleotide therapy and gene therapy?

Oligonucleotide therapy modulates RNA without altering DNA, while gene therapy introduces or edits genes to create lasting changes in how cells produce proteins.

How are oligonucleotide therapeutics delivered?

Certain oligonucleotide therapeutics can be delivered alone, while some require delivery using delivery systems—such as GalNAc or targeted peptides—to guide them precisely to relevant organs and cell types.

What are recent advances in oligonucleotide therapeutics?

Advances in oligonucleotides include improved tissue-targeted delivery, novel chemistries, innovative discovery approaches using AI, and broadening applications across many therapeutic areas and expanding availability of precise, patient-centred treatment options.

Are you a clinical trial participant?

If you are looking for trial information, please visit our clinical trials website: www.astrazenecaclinicaltrials.com.

Collaborate with us

We work with leading partners across academia, industry, scientific community and patient groups to help accelerate innovative approaches to medicine.

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Innovate with us

Join us as we work to advance oligonucleotide therapies designed to precisely target the biology that drives disease. Be part of an exciting and meaningful effort to help expand what’s possible for patients through the next generation of innovative medicines.

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Veeva ID: Z4-83253
Date of preparation: July 2026