Nanobodies are single-domain antibodies (sdAbs) consisting of the variable portion of the heavy chain responsible for binding with antigen epitopes. They exhibit enhanced affinity, stability, and penetration. However, nanobodies are only found in camelids and sharks, which makes them difficult to develop in vivo with traditional antibody discovery methods.
This is a nanobody (green) bound to a human tau protein (orange) which we classified as a pocket binding site. This was the nanobody used as a base for construction of our pocket binding library.
This is a nanobody (purple) bound to SARS-CoV-2 Spike Protein S1 (green) which we classified as a protrusion binding site. This nanobody was used as a base for construction of our protrusion binding library.
Above are the amino acid sequences of our base nanobodies. We identifies conserved regions by sorting all known nanobodies from the Protein Data Bank based on binding morphology and aligning the resulting groups respectively. The conserved regions are highlighted in red. The variable complimentary-determining regions (CDRs) were also identified and highlighted in green. This is where we introduced targeted mutations.
Credit: Baylee Larson