Antibody-Oligonucleotide Conjugates (AOCs)

Antibody-oligonucleotide conjugates are hybrid molecules that combine the targeting precision of antibodies with the functional versatility of therapeutic oligos. The antibody component homes in on targeted cells, while the oligo modulates gene expression once delivered. This mechanism allows for precise intervention at the molecular level in diseases that are challenging to treat with conventional approaches.

Using validated conjugation and analytical methods, we have over 20 years of expertise to ensure each AOC and bioconjugate that we design, develop and manufacture is consistent, pure, and ready for regulated development.

There are several key differences between AOCs and ADCs. There are unique chemical complexities of integrating antibody and oligonucleotide components into effective, manufacturable AOCs. AOC design and development factors include payload complexity, impurity profiles, and essential analytical methods.

Developing AOCs involves navigating an ever-changing and incomplete regulatory landscape. There is well established regulatory guidance for small molecules, biologics, and ADCs. However, the unique characteristics of AOCs, and particularly their oligo payloads, present challenges that existing frameworks do not completely address. This gap that exists requires AOC developers such as Abzena to adopt proactive and scientifically rigorous approaches. By partnering with experienced suppliers and consultants, and global regulatory bodies Abzena is well-positioned to navigate this challenging, changing landscape.

Because of their high-precision, AOCs are already redefining the boundaries of therapies to tackle diseases rooted in genetic dysfunction. The combination of oligos’ ability to modulate gene expression alongside antibodies’ cell-specific targeting, is creating opportunities to treat conditions previously considered intractable.

An oligonucleotide is a short DNA or RNA molecule. Custom synthesized in a lab, oligos can either be single- or double-stranded, which includes antisense oligonucleotides, RNA interference, and aptamer RNAs. When linked to a monoclonal antibody (mAb), Antibody-Oligonucleotide Conjugates (AOCs) provide a pathway for highly precise treatments. AOCs are particularly well-matched for diseases requiring targeted modulation of gene expression.