Summary
Wildtype (antibody) frameworks can accommodate CDRs that bind to virtually any antigen (1–2). This was demonstrated by De novo antibody design efforts that kept the framework sequence fixed while varying the CDRs, and is consistent with the fact that transgenic mice with only a single VH gene can still make effective antibodies against many targets.
1.
Bennett NR, Watson JL, Ragotte RJ, Borst AJ, See DL, Weidle C, et al. Atomically accurate de novo design of antibodies with RFdiffusion. Nature. 2025;649(8095):183–93. Available from: https://doi.org/10.1038/s41586-025-09721-5
2.
Mille-Fragoso LS, Driscoll CL, Wang JN, Dai H, Widatalla T, Zhang JL, et al. Efficient generation of epitope-targeted de novo antibodies with Germinal. openRxiv; 2025. Available from: https://doi.org/10.1101/2025.09.19.677421
3.
Stark H, Faltings F, Choi M, Xie Y, Hur E, O’Donnell T, et al. BoltzGen: Toward Universal Binder Design. openRxiv; 2025. Available from: https://doi.org/10.1101/2025.11.20.689494