Nanobodies are particularly attractive for development into therapeutics because they are easy to produce and bioengineer. In addition, they feature high stability and solubility and can be aerosolized and inhaled rather than administered through intravenous infusions, like traditional antibodies.
Highlights
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Proteomic pipeline for identification and quantification of camelid nanobody repertoires
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Discovery of thousands of distinct and high-affinity antigen-specific nanobody families
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Global epitope mapping by integrative structural proteomics
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Mechanisms underlying high-affinity antigen-nanobody binding
Nanobodies are particularly attractive for development into therapeutics because they are easy to produce and bioengineer. In addition, they feature high stability and solubility and can be aerosolized and inhaled rather than administered through intravenous infusions, like traditional antibodies.
Shi et al. developed a proteomic strategy to survey, at an unprecedented scale, the landscape of antigen-engaged, circulating nanobodies. Using high-throughput structural modeling, cross-linking mass spectrometry, mutagenesis, and deep learning, they mapped and analyzed the epitopes of hundreds of thousands of antigen complexes. They found that nanobodies can mimic conserved intracellular protein-protein interactions.
Mature nanobodies were first isolated from the llama blood based on their ability to bind specifically to the target of interest. Researchers then broke the antibodies into peptides, which were then analyzed via mass spectroscopy. Once the mass was determined, scientists can figure out their amino acid sequence. Then, from the amino acids, the researchers can work backward to DNA, enabling the creation of more nanobodies.
Then, using artificial intelligence software, the sequences are evaluated, determining which nanobodies have the highest affinity to pathogen and the epitope. These nanobodies are then mass-produced using recombinant technology.
"Using this new technique, in a matter of days, we're typically able to identify tens of thousands of distinct, highly potent nanobodies from the immunized llama serum and survey them for certain characteristics, such as where they bind to the pathogen," Shi said. "Prior to this approach, it has been extremely challenging to identify high-affinity nanobodies." (2)
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2.) Cheap, potent pathway to pandemic therapeutics