Linking up to reveal novel drug delivery solutions

Oligonucleotide conjugates offer the potential to deliver the oligonucleotide to a specific cell or tissue and thus reduce the amount of drug required to treat disease in patients. Conjugation of oligonucleotides to targeting ligands can also improve the pharmacokinetic properties of oligonucleotides (short therapeutic RNA or DNA molecules) and expand their scope of application.1

Linking a small molecule, peptide, carbohydrate, or antibody to oligonucleotides through conjugation are approaches already being used in research applications, such as qPCR, sequencing and hybridisation, and in fluorescence dyes for microscopy. New advances in linker chemistry and drug delivery technologies that can improve stability and uptake into target cell types are now emerging as potential tools to fuel the growing interest in the therapeutic application of oligonucleotides.

Conjugated oligonucleotides are an exciting approach for delivery of nucleic acid therapeutics to specific cells and tissues. Access to novel targeting conjugates provides the opportunity for precise modulation of disease targets and expansion of the target space across therapy areas.

Shalini Andersson Chief Scientist & Head of Oligonucleotide Discovery, Discovery Sciences, R&D

The linker chemistry is designed so that the conjugate cleavage occurs in the desired cell type to deliver the drug where it can modulate the disease-causing target. The linker design is also critical in limiting the risk of toxicity driven by the linker fragments that may be released upon conjugate cleavage or degradation.2,3


1. Winkler J. Oligonucleotide conjugates for therapeutic applications. Ther Deliv. 2013;4(7):791-809.

2. Seth PP, Tanowitz M, Bennett CF. Selective tissue targeting of synthetic nucleic acid drugs. J Clin Invest. 2019;129(3):915-925.

3. Ämmälä C, Drury WJ 3rd, Knerr L, et al. Targeted delivery of antisense oligonucleotides to pancreatic β-cells. Sci Adv. 2018;4(10):eaat3386. Published 2018 Oct 17.

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