AstraZeneca shows potential of gene silencing in pancreatic cells

Research published in Science Advances shows first functional delivery of antisense oligonucleotides to pancreatic beta-cells in vivo

AstraZeneca today announced breakthrough research that enables genes to be ‘silenced’1 specifically in insulin-secreting pancreatic beta-cells using targeted delivery of antisense oligonucleotides (ASOs) in in vivo models. This represents the first example of targeted delivery of ASOs to a tissue other than the liver and opens the possibility of this drug modality to develop future treatments for a broader array of diseases. The pioneering approach was led by AstraZeneca’s Innovative Medicines and Early Development (IMED) Biotech Unit and was published in Science Advances.1

ASOs are a drug modality with disease-modifying therapeutic potential which has historically been limited by delivery challenges since they are too large to passively diffuse into cells and many cell types will not actively internalise them.2 This new research demonstrates how uptake of ASOs into pancreatic beta-cells can be enabled by tagging them to a protein (peptide conjugation) recognised and internalised by the glucagon-like peptide 1 receptor (GLP1R) which is highly expressed on pancreatic beta-cells.1

Researchers found in preclinical models the ASO target gene in the beta-cell could be silenced without affecting gene expression in other cells in the pancreas, liver or other tissues. This indicated that this technique is highly specific for cell types expressing GLP1R.

Carina Ämmälä, Team Leader in Cardiovascular, Renal and Metabolism (CVRM) at AstraZeneca’s IMED Biotech Unit, and lead scientist on the study said: “This pre-clinical proof-of-concept study opens new possibilities for the use of ASOs to treat diseases affecting pancreatic beta-cells, such as type-2 diabetes. Current available treatments for diabetes can control the symptoms but do not modify the disease and most patients experience a progressive loss of functional beta-cells leading to reduced insulin secretion and worsening of the disease. Our goal is now to further explore the possibility of using targeted delivery ASOs to create a regenerative treatment that could restore beta-cell function.”

The study was conducted as part of AstraZeneca’s collaboration with Ionis Pharmaceuticals to discover and develop novel antisense therapies for cardiovascular, renal and metabolic diseases.

Brett Monia, Ph.D., chief operating officer at Ionis said: “This work highlights the potential of Ionis’ antisense technology and its ability to potentially deliver targeted antisense oligonucleotides to specific cell types throughout the body, cells that were previously considered unreachable. Through our collaboration with AstraZeneca, we are making great progress towards discovering new ways of getting life-changing therapeutics to patients.”

About Antisense oligonucleotides (ASOs)

ASOs are a new class of therapeutic molecules. They are short, chemically modified, single-stranded nucleic acids that can target any gene product of interest.

ASOs offer new opportunities for therapeutic intervention because they act inside the cell to influence protein production. They do this by targeting ribonucleic acid (RNA) to either prevent the production of disease-causing proteins, increase the production of proteins deficient in disease, or target toxic RNAs that are unable to generate proteins. Antisense drugs are also able to target emerging biology mediated by microRNAs and long, non-coding RNAs. In recent years ASO-based treatments have been approved for spinal muscular atrophy and Duchenne muscular dystrophy.2

About IONIS Pharmaceuticals, Inc.

As the leader in RNA-targeted drug discovery and development, Ionis has created an efficient, broadly applicable, proprietary antisense technology platform with the potential to treat diseases where no other therapeutic approaches have proven effective. Our drug discovery platform has served as a springboard for actionable promise and realized hope for patients with unmet needs. We have a pipeline of more than 40 drugs with the potential to treat patients with cardiovascular disease, rare diseases, neurological diseases, infectious diseases and cancer.   

To learn more about Ionis, visit or @ionispharma on twitter.

About AstraZeneca IMED Biotech Unit

IMED Biotech Unit is one of two global research and early development arms of AstraZeneca, focusing on advancing small molecules, oligonucleotides and other emerging technologies and drug discovery platforms. The Biotech Unit conducts innovative discovery research and early-stage development from initial target selection to Phase II trial completion. The second global research and early development arm is MedImmune which is responsible for global biologics R&D, including immunotherapies.

About AstraZeneca

AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of diseases in three therapy areas - Oncology, Cardiovascular, Renal & Metabolism and Respiratory. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide.

For more information, please visit and follow us on Twitter @AstraZeneca.



1 Ämmälä C, et al. (2018). Targeted delivery of antisense oligonucleotides to pancreatic beta-cells. Science Advances 4(10): eaat3386

2 Kaczmarek J, et al. (2017). Advances in the Delivery of RNA Therapeutics: From Concept to Clinical Reality. Genome Medicine. 9:60.


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