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Veterinary Therapeutic Antibody Engineering
Veterinary therapeutic antibody engineering involves optimizing and adjusting the structure and function of antibody molecules, aiming to bring the samples closer to the desired effects when administered to animals. BioVenic has established a platform for engineering veterinary therapeutic antibodies, offering services such as antibody caninization, felinization, affinity maturation, and Fc engineering modification.
Antibody Caninization and Felinization
BioVenic offers antibody caninization and felinization services for murine-derived therapeutic antibodies, reducing the heterologous nature of murine-derived antibodies towards canines and felines. We aim to minimize the immunogenicity of heterologous antibodies while striving to maintain the antibodies' original affinity.
- Chimeric Antibody Technology
BioVenic has established a technology platform for chimeric antibodies. Leveraging chimeric antibody technology, the light and heavy chain variable regions of murine antibodies are subjected to genetic recombination. They are then fused with the constant regions of canine or feline antibodies to create a chimeric gene. BioVenic offers excellent mammalian cell antibody expression systems, including CHO cells and HEK293 cells, providing high-quality glycosylation and post-translational modifications. Additionally, we possess extensive experience in the development of chimeric antibodies across multiple species to meet various service requirements.
Fig.1 Antibody production workflow:from gene synthesis to quality control.(BioVenic Original)
- CDR Grafting
BioVenic offers CDR grafting services, which involve transplanting the CDRs from the original antibody onto a canine or feline framework. This process enhances the affinity and specificity of antibodies. During CDR grafting, we introduce revertant mutations to maintain the overall structural stability of the antibodies, ensuring that veterinary therapeutic antibodies fold correctly and retain their functionality while reducing the potential increase in inherent immunogenicity associated with CDR grafting.
Fig.2 CDR grafting and affinity maturation.1,2
Antibody Affinity Maturation
Antibody affinity refers to the strength of binding between the target antigen and the antigen-binding site. High-affinity antibodies can bind more rapidly, leading to better therapeutic effects when administered to animals. The process of felinization or caninization of therapeutic veterinary antibodies may lead to a decrease in antibody affinity. BioVenic provides antibody affinity maturation services to enhance the affinity of antibody samples through in vitro methods, resulting in improved performance. We offer a variety of mutation strategies that mimic the process of antibody affinity maturation in vivo.
| Services | Description |
|---|---|
| Error-Prone PCR | Random mutants may be inserted into any piece of DNA by reducing the fidelity of the DNA polymerase. The random mutagenesis was repeated through multiple rounds of PCR to accumulate the mutation effect and finally obtain the random mutant of the target protein. |
| DNA shuffling | The DNA fragments are cut into smaller fragments, usually no more than 50bp, and then randomly rearranged and recombined by exchanging and fusing the DNA fragments, after which these new sequences are PCR-amplified into complete antibody genes. |
| Site-Directed Mutagenesis | Somatic high-frequency mutations usually occur in the CDR region of the antibody that interacts directly with the antigen, and therefore the CDR is usually chosen as a specific target for targeted mutations. |
| Computational Approaches | Optimize antigen-antibody interactions based on antibody modeling and prediction of design mutation changes. |
- Phage Display Library Screening
BioVenic provides phage display library screening services. Based on phage display technology, we construct large-capacity mutation libraries and perform biopanning of antibodies to obtain antibodies with significantly improved affinity.
- Antibody Expression
BioVenic provides antibody expression services. Using the various antibody expression system we have established, such as mammalian cell expression systems, the recombinant proteins obtained by expression are close to the natural conformation and have good biological activity.
- Antibody Affinity Assays
BioVenic offers antibody affinity assays to validate the results of veterinary therapeutic antibody affinity maturation. With these techniques, we measure the binding affinity and kinetics of antibody-antigen interactions, helping to assess the applicability of antibodies for therapeutic use in animals.
| Surface Plasmon Resonance (SPR) | Isothermal Titration Calorimetry (ITC) |
| Enzyme-Linked Immunosorbent Assay (ELISA) | Biological Layer Interferometry (BLI) |
Fc Engineering Modification
The extension of the half-life of therapeutic antibodies in veterinary applications not only enhances efficacy but also reduces dosing frequency. The crystallizable fragment (Fc region) is composed of the heavy chain constant region and mediates cellular effector functions. Modifying the Fc segment can prolong the presence of therapeutic antibodies in the bloodstream. BioVenic provides Fc engineering services, employing amino acid mutations on the Fc region to enhance its binding affinity with FcRn at pH 6.0 conditions. This modification aims to extend the antibody's half-life while maintaining pH-dependent effects.
| Alanine Scanning | Directed Mutagenesis |
| Molecular Simulation | Random Mutagenesis |
Why Choose Us?
We offer antibody caninization and felinization services in conjunction with our antibody affinity maturation services.
We provide multiple mutagenesis strategies for you to choose from to maintain high affinity in veterinary therapeutic antibodies.
Our advanced mammalian cell antibody expression and phage display screening technology platform ensures a fast and high-throughput process.
We offer a variety of methods to assist you in extending the half-life of veterinary therapeutic antibodies.
Murine-derived antibodies can trigger immune responses, reducing the efficacy of veterinary therapeutic antibodies during treatment. BioVenic provides antibody caninization and felinization services, helping reduce the immunogenicity and minimize the risks associated with heterologous antibodies. Our affinity maturation services enhance the binding affinity of antibodies to specific antigens, increasing their clearance efficiency in the body. Our Fc engineering modification services extend the antibody half-life, ultimately improving therapeutic outcomes. If you're interested in veterinary therapeutic antibody engineering, please contact us!
References
- Wagner, Hanna J., et al. "A two-step approach for the design and generation of nanobodies." International journal of molecular sciences 19.11 (2018): 3444.
- Image retrieved from Figure 1 "Schematic overview of a two-step approach for the generation of VHH.",Wagner, Hanna J., et al., 2018, used under [CC BY 4.0], the image title was changed to "CDR grafting and affinity maturation."