Antibody Conjugate-Based Delivery Systems

Antibodies have been used as delivery vehicles for many kinds of drugs by conjugating them with these drugs. This approach of direct conjugation has been extended to oligonucleotide therapeutic delivery. Specific interaction between an antibody and a cell surface receptor has the potential to enable oligonucleotide therapeutic delivery to tissues and/or cell subpopulations. Various receptors have been successfully targeted for siRNA delivery, including the HIV gp160 protein, HER2, CD7 (T cell marker), CD71 (transferrin receptor, highly expressed in cardiac and skeletal muscle) and TMEFF2. Similarly, ASOs have also been conjugated with antibodies against CD44 (a neural stem cell marker), EPHA2 and EGFR^[1].

Synthetic Approaches of Antibody-Oligonucleotide Conjugates

The following two approaches are commonly used to prepare antibody-oligonucleotide conjugates:

Non-covalent Approach

Non-covalent antibody-oligonucleotide conjugates are modular structures in which monoclonal antibodies and oligonucleotide molecules are non-covalently linked by special linkers. The main advantage of this approach is its general applicability and universality, as it does not require conjugation and purification steps to be conducted and can therefore be performed with a low amount of readily available antibodies.

Covalent Approach

The covalent approach enables stable linkages in antibody-oligonucleotide conjugates and affords more defined structures. The classic method for preparing antibody-oligonucleotide conjugates is to conjugate oligonucleotides to either lysine residues, present in native antibodies, or cysteine residues.

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Alfa Chemistry is proficient in the drug delivery technology of oligonucleotide therapeutics and provides solutions to improve the delivery efficiency and security of oligonucleotide therapeutics. You can also contact us directly to customize antibody-oligonucleotide conjugates to speed up your project.

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