Antibody-Oligonucleotide Conjugates (AOC) Development Services

Antibody-oligonucleotide conjugates (AOCs) are a novel class of synthetic chimeric biomolecules that has been continually gaining traction in different fields of modern biotechnology. Creative Biolabs focuses on developing this new class of oligonucleotide conjugates to overcome the current limitations of oligonucleotide (ON) therapies for a wide range of serious diseases. Base on our perfect AOC platform, AOCs can be designed, engineered, and developed to combine the tissue and disease selectivity of monoclonal antibodies (mAbs) and the precision of oligonucleotide-based therapies to access previously undruggable tissue and cell types, and more effectively target underlying genetic drivers of diseases. Creative Biolabs provides comprehensive AOC development services for our honor clients and the AOCs candidates derived from our platform will have the potential to offer distinct advantages over ON itself.

AOC Introduction

Combining different functionalities in one entity by generating chimeric constructs has always been an attractive strategy in various fields such as biology, chemistry, and medicine. Two important families of biomolecules have gained a lot of attention and have already revolutionized the field of diagnostics and therapeutics, they are mAbs and Oligonucleotide Synthesis (ONs). Combining the distinct functionalities of mAb and ON in one chimeric construct (namely AOC) has been explored. The AOC constructs can trigger complex biological mechanisms ranging from immune responses to cell differentiation, apoptosis, and protein expression, thus AOC attracted a lot of interest in both academic and industrial fields.

Conjugation Strategies of AOC Development

Similar to antibody-drug conjugation, ONs can be attached to different sites of an antibody using diverse conjugation chemistry. Multiple endogenous amino acids can serve as potential conjugation sites. Antibody and ON could be conjugated via different covalent and noncovalent conjugation strategies. Among them, amine conjugation, sulfhydryl conjugation, and carbohydrate conjugation are the most known three methods.

• Amine Conjugation

Antibodies contain several amino groups (NH₂), which can be distributed throughout as lysine side chain epsilon-amine and N-terminal alpha-amino groups. These residues are most often targeted for conjugation as they can easily be modified owing to their steric accessibility. Besides amino groups, glutamic acid, aspartic acid residues, and carboxylic acid can also be conjugated.

• Sulfhydryl Conjugation

Antibody-ON conjugation is also possible via a reactive thiol (sulfhydryl) group. Antibodies contain oxidized sulfhydryl (-SH) groups present as disulfide (S-S) bridges and these disulfide bridges must be reduced first to expose their reactive groups by a reducing agent

• Carbohydrate Conjugation

An alternative method of site-directed conjugation can occur at carbohydrate residues, which occurs mainly in the Fc region because they are less susceptible to steric hindrance due to their remoteness from antigen-binding sites. For conjugation via this complex method, the carbohydrate group must be oxidized to an aldehyde (-CHO) using periodic acid. An advantage is that AOCs produced via site-specific conjugation techniques have distinct advantages for in vivo applications.

Fig.1 A schematic diagram of the antibody-ON conjugation process. (Soler Aznar, 2015)

Application of AOCs

In AOC complex, the antibody is usually employed as a target recognition unit or delivery vehicle and the ON serves in a variety of functional roles such as scaffold for spatial arrangement or therapeutic drug (small interfering RNA, siRNA). AOCs have been used in numerous applications ranging from diagnostics to therapeutics and were developed through an unmet need for precise and efficient detection of low-abundance proteins. AOCs have since played a significant role in immuno-polymerase chain reaction (iPCR), proximity extension assay (PEA), electrochemical proximity assay (ECPA), DNA-PAINT imaging, and protein arrays. Based on the exceptional ability of PCR to amplify the number of DNA labels and the transformation of readily accessible ON-arrays into otherwise difficult to access antibody arrays, AOCs can largely improve the detection limits.

What Can We Do for You?

Creative Biolabs takes full advantage of our featured platform to develop a portfolio of AOCs that combine the selectivity of mAbs and the precision of oligonucleotide therapy and diagnosis. Our deep experience with modulation of RNA processes, oligonucleotide therapeutics, mAb engineering and conjugation, and various drug delivery techniques provide the foundation for our efforts to promote your novel AOC development. The know-how and advanced technology born out of this experience, and their systematic application in the design and development of our product candidates, form the basis of our AOC development platform. Based on our platform, our scientists have also established a framework for screening potential cell surface protein-mAb pairs to determine which pairs we believe are well suited to deliver active ONs to specific cell types.

Our goal is to help clients discover, develop and commercialize novel AOCs that overcome current barriers to the delivery of ONs and unlock their potential to treat or diagnose diseases currently lacking adequate treatment or detection options. Based on the data-driven hypothesis that the delivery of ONs can be greatly enhanced by using antibodies as conjugates, Creative Biolabs offers high-quality AOCs development services for our global clients. If you are interested in our AOC development services, please feel free to contact us for more information.

Reference

1. Soler Aznar, M. Nanoplasmonic biosensors for clinical diagnosis at the point of care. Universitat Autònoma de Barcelona. 2015.

For Research Use Only. NOT FOR CLINICAL USE.