Precise ncAA placement for targeted antibody engineering
Random conjugation at native lysine or cysteine residues often produces antibody-drug conjugates (ADCs) with inconsistent drug-to-antibody ratios (DARs), reduced stability, and variable therapeutic outcomes. Our site-specific incorporation strategy overcomes these limitations by introducing non-canonical amino acids (ncAAs) with tailored chemical reactivity at predetermined positions within the antibody structure. The result is a homogeneous, stable, and functionally optimized antibody product.
Advantages at a Glance
- Uniform DAR Control – Achieve reproducible and predictable pharmacokinetics.
- Preserved Functionality – Maintain natural folding, stability, and antigen-binding affinity.
- Expanded Chemical Diversity – Incorporate azides, ketones, alkynes, or other orthogonal groups.
- Improved Safety – Reduce off-target toxicity through precise molecular design.
- Enhanced Stability – Integrate moieties that extend serum half-life without impacting potency.
Key Application Areas
✅ Homogeneous ADC Development
Install ncAAs equipped with bioorthogonal handles for reproducible and quantitative drug loading. This eliminates DAR variability and supports streamlined manufacturing.
✅ Bispecific Antibody Construction
Encode complementary reactive chemistries in different antibody chains to guide accurate directional assembly. This improves correct pairing rates and minimizes purification challenges.
✅ Long-Acting Antibody Engineering
Introduce PEGylation handles or stability-enhancing groups in the Fc domain to extend circulation time while maintaining antigen-binding activity.
Our Process
1) Consultation & Site Selection – Define sequence, modification sites, and functional goals.
2) Genetic Engineering – Incorporate codons for ncAA insertion at precise positions.
3) ncAA Selection – Choose from a curated portfolio of functional ncAAs.
4) High-Fidelity Expression – Use orthogonal tRNA/aaRS systems in bacterial or mammalian hosts.
5) Purification & QC – Employ advanced chromatography and LC-MS to confirm structural accuracy.
6) Final Delivery – Provide purified antibody, full analytical data, and documentation.
Why Choose Us
- Proven Accuracy – DAR variation typically under 5%
- Diverse ncAA Library – Supports multiple conjugation chemistries
- Flexible Scale – From discovery to pilot manufacturing
- Comprehensive Quality Checks – Mass spectrometry and functional testing included
- Custom Strategies – Tailored solutions for complex antibody formats
