We strongly recommend the immediate manual selection and rigorous experimental evaluation of our highly refined portfolio of ten novel nanobody sequences, which were meticulously engineered based on robust, clinically validated structural scaffolds derived from the latest commercial and clinical-stage nanobody therapeutics, thereby ensuring inherent stability and optimal pharmacological profiles for genuine therapeutic applications; this focused engineering effort centered specifically on optimizing the three Complementarity-Determining Regions (CDRs)—the critical binding loops—to confer specific, high-affinity antigen recognition capabilities that advance beyond simple in silico homology screening. Crucially, the design methodology integrated the advanced generative power of Boltz-Gen for expansive sequence space exploration with the proprietary, in-house structure prediction model, DynaHelix, which is specifically optimized for enhancing prediction precision by pioneering the automated search across diverse potential interface configurations during the modeling process, thereby mitigating the limitations of static structural predictions and identifying the most viable binding geometry; despite the fact that the resulting CDR-antigen interaction interfaces might initially exhibit lower scores in standard metrics such as interface predicted Template Modeling score (iptm) or Predicted Aligned Error (PAE)—a common and expected outcome when generating novel sequences outside of known structural datasets—we maintain that the depth of the structure-centric validation and multi-model optimization warrants their selection, as it prioritizes functional feasibility and the probability of a therapeutic mechanism over raw predictive statistics; consequently, these ten structure-guided candidates offer truly novel binding modalities and structural solutions that demand expert appraisal and represent a significant strategic opportunity to accelerate the development of next-generation nanobody therapeutics.