Polymer-Conjugated Antisense Oligonucleotide (ASO) Development Service

Introduction

Polymer-conjugated antisense oligonucleotides (ASO) exhibit enhanced drug stability and solubility, controllable drug delivery, improved efficacy and pharmacokinetics. Creative Biolabs has professional technical personnel in polymer-conjugated ASO and can provide personalized one-stop service to help customers solve related problems with ASO conjugates.

Overview of Polymer-conjugated ASO

The polymers can be conjugated to ASO by streptavidin/biotin interaction, covalent bonds, electrostatic interactions, and other mechanisms. Direct covalent conjugation is the most commonly used method, and the specific conjugation mode depends on the type of polymer and the chemical properties of ASO. For example, it is possible to use functional groups on polymers (such as amino groups, carboxyl groups, etc.) to react with functional groups on ASO (such as phosphate groups, amino groups, etc.) to form covalent bonds.

Applications

PEG offers numerous advantages, including biocompatibility, lack of immune response stimulation, and excellent water solubility. In the biomedical field, PEG is often used as a drug carrier, modifier, or coating material to improve the solubility, stability, and bioavailability of drugs. Some studies of PEG-conjugated ASO have shown that a 20 kDa PEG coupled to a releasable linker at the 5'-terminus of the ASO shows better pharmacokinetics than the unmodified ASO. In addition, pegylation protects the conjugated molecules from degrading enzymes and reduces their nonspecific interactions with proteins, reducing ASO renal excretion, and thereby improving their blood stability and retention time.

Fig.1 PEG^1,3

A novel platform for tetravalent conjugating of 4-armed PEG and ASO has been developed². Multivalent drug molecules conjugated with PEG hold high promise because the addition of multiple ligands can increase the local concentration of the ligand and enable it to have multiple simultaneous interactions with biological targets. The quadruple conjugate has the ability to hybridize with complementary RNA, and the advantage is that it can enter cells in the absence of transfection reagents, which reduces the risk of toxicity of transfection reagents to cells, can effectively silence target genes, and has long-term stability in cell extracts.

Fig.2 4-arm PEG^2,3

Applications of polymer-conjugated ASO include:

Gene therapy: By specifically binding to target genes and inhibiting their expression, so as to achieve the purpose of treating diseases.

Molecular diagnostics: The ability of ASO to bind to specific DNA or RNA sequences is used for early diagnosis and screening of diseases.

Biological analysis: In biological studies, polymer-conjugated ASO can be used as probes or primers for DNA sequencing, gene cloning, and other experiments.

Advantages

Improved stability: The polymer enhances the resistance of ASOs to the nuclease and prolongs the half-life of drugs.

Enhanced targeting: Targeted delivery to specific cells or tissues can be achieved by choosing the appropriate polymer and conjugation modality.

Improved biological activity: Polymer-conjugated ASO may have higher biological activity and more effective inhibition of target gene expression.

Polymer-conjugated ASO has a wide range of potential applications in biotechnology and medicine. Creative Biolabs develops a variety of polymer conjugation methods to help customers achieve efficient and safe ASO delivery and treatment processes. If you are interested in the content of polymer-conjugated ASO, please feel free to contact us, we will be pleased to provide service.

References

1. Chen, Xuecheng, and Rudolf Holze. "Polymer Electrolytes for Supercapacitors."Polymers 16.22 (2024): 3164.
2. Chowdhury, Taslima Rahman, et al. "Synthesis and biophysical properties of tetravalent PEG-conjugated antisense oligonucleotide." Bioorganic & Medicinal Chemistry 78 (2023): 117149.
3. Distributed under Open Access license CC BY 4.0, without modification.