Humanization
The humanization of nanobodies is crucial for the development of therapeutic nanobody drugs. The sdAb-GPT platform developed by Jotbody offers camelid-derived nanobody humanization services based on generative AI, reducing the immunogenicity of non-human antibodies while ensuring that humanized antibodies maintain comparable activity to the original antibodies, enhancing affinity and expression levels, and improving stability and solubility.
The sdAb-GPT platform extensively trains the GPT model on a large dataset of nanobody data, accurately capturing the complex relationship between complementarity-determining regions (CDRs) and framework regions (FRs), and learning to generate such antibodies. By employing carefully designed reinforcement learning methods, this model generates nanobody sequences that meet multiple development standards in a single iteration and combines structural modeling to select humanized nanobodies with optimal performance.
Technical Process
Platform Advantages
| sdAb-GPT Platform | Traditional Humanization Methods |
|---|---|
| Sequence analysis and generation based on GPT | Homology modeling of antibodies |
| Molecular simulation for structure and function prediction | Replacement of antibody FR framework regions |
| Multi-target fine-tuning to enhance antibody performance | Amino acid revertant mutation analysis |
| No need for revertant mutations | |
| Immunogenicity and PTM prediction |
Service Offerings and Duration
| Stage | Service Content | Duration | Deliverables |
|---|---|---|---|
| I | Sequence analysis | 3–4 days | Use GPT generative algorithm to analyze nanobody sequences and structures in depth to identify potential immunogenic regions |
| II | Framework generation | Generate human antibody frameworks that best match the nanobody CDR region structurally, reducing immunogenicity while preserving the original antibody’s performance as much as possible | |
| III | Structure prediction | 1 week | Based on homology modeling to predict the structure and function of humanized antibodies, verify their binding ability and stability with antigens; predict immunogenicity, PTM sites, etc. |
| IV | Expression and purification | 3–4 weeks | Express and purify 5–10 humanized antibodies, evaluate production performance, provide ~0.1 mg per antibody, purity ≥90% |
| V | Activity verification | 1–2 weeks | Rank antibody molecular affinity to ensure on the Biacore detection level, antibody affinity is at least 3 times that of the original antibody |
Deliverables: 5–10 sequences of humanized antibodies, purified proteins, final project report including data analysis of all the above steps.
Total Duration: 5–6 weeks.
Case Study
