Antibodyoligonucleotide

Antibody-oligonucleotide conjugates represent a novel class of therapeutic agents that combine the targeting specificity of antibodies with the gene-regulatory or gene-silencing capabilities of oligonucleotides. These hybrid molecules are designed to deliver short interfering RNA (siRNA), antisense oligonucleotides (ASOs), or other nucleic acid sequences directly to specific cells or tissues, thereby enhancing therapeutic efficacy while minimizing off-target effects.

The development of antibody-oligonucleotide conjugates builds upon the success of antibody-drug conjugates (ADCs), which have been widely used in oncology. In these constructs, an antibody is chemically linked to an oligonucleotide via a stable linker. The antibody component binds to a cell-surface antigen overexpressed on target cells, facilitating internalization of the oligonucleotide upon binding. Once inside the cell, the oligonucleotide can exert its intended effect, such as knocking down a disease-causing gene or modulating gene expression.

A key advantage of antibody-oligonucleotide conjugates is their potential to overcome barriers associated with systemic oligonucleotide delivery, such as rapid degradation by nucleases or poor cellular uptake. By leveraging the natural endocytic pathways of antibodies, these conjugates can improve intracellular delivery efficiency. Additionally, they may reduce the need for high systemic doses, thereby lowering toxicity risks.

Research in this area has focused on applications in oncology, where targeting oncogenes or tumor-associated antigens with siRNA or ASOs could provide precise and potent therapeutic effects. Preclinical studies have demonstrated the feasibility of this approach, though challenges remain in optimizing linker stability, conjugation efficiency, and immune responses. As the field evolves, antibody-oligonucleotide conjugates hold promise as a versatile platform for treating a range of diseases, including genetic disorders and autoimmune conditions.