Llamanade

Llamanade performs rational humanization of nanobodies (Nbs) by analyzing their sequence and structural properties to guide modifications that increase humanness while preserving solubility, stability, and antigen-binding activity.

Key Features:

• Systematic sequence and structural analysis: Comprehensive analysis of Nb sequence and structural properties is performed using next-generation sequencing (NGS) databases and high-resolution structures.
• Framework diversity assessment: Identifies significant framework differences between camelid-derived Nbs and human Immunoglobulin G (IgG) antibodies.
• Conserved residue identification: Detects conserved residues that contribute to solubility, structural stability, and antigen-binding capabilities to inform humanization choices.
• Computational efficiency: The pipeline is designed for rapid processing of individual Nb sequences.
• Demonstrated robustness on viral neutralizers: Applied to a cohort of structurally diverse SARS-CoV-2 neutralizing Nbs, increasing humanness while maintaining solubility and bioactivity.

Scientific Applications:

• Therapeutic nanobody development: Guides sequence and structure modifications to advance Nbs toward therapeutic candidates.
• Improving translational potential: Increases humanness of camelid-derived Nbs to reduce xenogeneic risk and enhance suitability for clinical development.
• Optimization of biophysical and binding properties: Supports maintenance or improvement of solubility, stability, and antigen-binding during humanization.

Methodology:

Performs big data analysis integrating sequence and structural insights from extensive Nb databases, including next-generation sequencing (NGS) databases and high-resolution structures, within a computational humanization pipeline.