Related Experiment Video

Updated: Feb 3, 2026

Intrathecal Delivery of Antisense Oligonucleotides in the Rat Central Nervous System
07:47

Intrathecal Delivery of Antisense Oligonucleotides in the Rat Central Nervous System

Published on: October 29, 2019

19.7K

Targeted delivery of antisense oligonucleotides to pancreatic β-cells

C Ämmälä1, W J Drury1, L Knerr1

  • 1Cardiovascular Renal and Metabolic Diseases, IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden.

Science Advances
|October 23, 2018
PubMed

Insights

Targeted delivery of antisense oligonucleotides (ASOs) to pancreatic beta cells was achieved by conjugating ASOs to a glucagon-like peptide-1 receptor (GLP1R) ligand, enhancing therapeutic potential.

Area of Science:

  • Biotechnology
  • Molecular Biology
  • Pharmacology

Background:

  • Antisense oligonucleotides (ASOs) offer a novel therapeutic strategy for silencing disease-associated genes.
  • Current ASO delivery methods face limitations, with preferential accumulation in the liver and kidney, and poor uptake by pancreatic beta cells.

Purpose of the Study:

  • To develop a targeted delivery method for ASOs to pancreatic beta cells.
  • To investigate the efficacy and specificity of ASO delivery mediated by a glucagon-like peptide-1 receptor (GLP1R) ligand.

Main Methods:

  • Conjugation of ASOs to a GLP1R-targeting ligand.
  • In vitro and in vivo studies to assess ASO delivery and gene silencing in pancreatic beta cells.
  • Evaluation of gene expression in pancreatic islets, liver, and other tissues.

Main Results:

  • GLP1R-ligand conjugated ASOs successfully delivered cargo to pancreatic beta cells both in vitro and in vivo.
  • Target gene silencing was observed in pancreatic islets at specific doses.
  • Enhanced tissue and cell type specificity was demonstrated, with no significant effect on gene expression in the liver or other tissues.

Conclusions:

  • Conjugating ASOs to GLP1R ligands provides a novel and effective strategy for targeted delivery to pancreatic beta cells.
  • This approach broadens the therapeutic applications of ASO technology.
  • The method presents an innovative platform for targeted ASO delivery to various cell types.

More Related Videos

Microinjection of mRNA and Morpholino Antisense Oligonucleotides in Zebrafish Embryos.11:33

Microinjection of mRNA and Morpholino Antisense Oligonucleotides in Zebrafish Embryos.

Published on: May 7, 2009

37.6K
Multi-exon Skipping Using Cocktail Antisense Oligonucleotides in the Canine X-linked Muscular Dystrophy10:30

Multi-exon Skipping Using Cocktail Antisense Oligonucleotides in the Canine X-linked Muscular Dystrophy

Published on: May 24, 2016

19.2K

Related Concept Videos

Target Cell Response to Hormones01:22

Target Cell Response to Hormones

Hormones intricately bind to receptors on the surface or within target cells, initiating a cascade of cellular responses.
Notably, the cellular response can be regulated by altering the number of receptors expressed in the cell. For example, prolonged exposure to elevated hormone levels results in a gradual decline or down-regulation in the number of receptors for that specific hormone on the cell surface. Conversely, in response to low hormone levels, cells may use up-regulation, producing an...
5.7K
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
10.5K
Pancreatic Juice and Secretion01:26

Pancreatic Juice and Secretion

Pancreatic juice is a clear fluid produced by the pancreas, containing water, salts, sodium bicarbonate, and enzymes vital for digestion in the small intestine. It helps break down large molecules, facilitating nutrient absorption.
When acidic chyme from the stomach enters the duodenum, it triggers the release of secretin, a hormone that prompts pancreatic juice secretion. After a fatty meal, cholecystokinin, another hormone, stimulates gallbladder contraction and enhances enzyme-rich...
3.0K
Acute Pancreatitis I: Introduction01:27

Acute Pancreatitis I: Introduction

Pancreatitis is inflammation of the pancreas, an organ located behind the stomach. It can be either acute or chronic.
Acute pancreatitis is characterized by rapid inflammation of the pancreas, often caused by factors like gallstone blockage or excessive alcohol consumption. Chronic pancreatitis, on the other hand, is a slow, progressive inflammation that may result from long-term alcohol abuse, obstructions in the pancreatic duct, or genetic factors.
The causes of acute pancreatitis include:
1.3K
Chronic Pancreatitis I: Introduction01:24

Chronic Pancreatitis I: Introduction

The pancreas, an elongated and flat gland situated behind the stomach, serves a vital function in digesting food and managing blood sugar levels.
Pancreatitis is the inflammation of the pancreas, which occurs when the immune system becomes active and causes swelling, pain, and disruptions in organ function. Pancreatitis can manifest as either an acute or chronic condition.
Acute pancreatitis arises suddenly and lasts for a brief duration, while chronic pancreatitis is a long-term affliction...
740
Adrenergic Receptors: β Subtype01:26

Adrenergic Receptors: β Subtype

β-adrenoceptors have varied sensitivities towards adrenaline, noradrenaline, and isoprenaline. The order of agonist potency is as follows:
Isoprenaline > Adrenaline > Noradrenaline
Neurotransmitter binding to these receptors causes activation of adenylyl cyclase resulting in increased concentrations of cAMP and modulation of calcium ion channels within the cell. They are further classified into β1, β2, and β3 subtypes.
β1-adrenoceptors: β1-adrenoceptors...
3.8K