期刊
CELL CHEMICAL BIOLOGY
卷 28, 期 9, 页码 1379-+出版社
CELL PRESS
DOI: 10.1016/j.chembiol.2021.05.019
关键词
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资金
- National Institutes of Health [RF1AG059723, R01AG050598, R35GM136300, U54GM103297, R21AI152865, R01 AI 151588 01]
- National Science Foundation (CBET) [1159943, 1605266, 1813963]
- Graduate Research Fellowship
- Biointerfaces Institute
- Albert M. Mattocks Chair
- MICHR Education PTSP [U069943]
- CVC Impact Research Ignitor Grant Award
- University of Michigan MICHR Accelerating Synergy Award
- University of Michigan Institutional Funds
- Directorate For Engineering [1813963] Funding Source: National Science Foundation
- Directorate For Engineering
- Div Of Chem, Bioeng, Env, & Transp Sys [1159943] Funding Source: National Science Foundation
- Directorate For Engineering
- Div Of Chem, Bioeng, Env, & Transp Sys [1605266] Funding Source: National Science Foundation
- Div Of Chem, Bioeng, Env, & Transp Sys [1813963] Funding Source: National Science Foundation
There is a strong interest in developing effective methods for generating neutralizing antibodies and nanobodies against SARS-CoV-2. This study presents a simple directed evolution method for producing nanobodies with high affinities and neutralization activities, which can effectively neutralize both SARS-CoV-2 pseudovirus and live virus.
There is widespread interest in facile methods for generating potent neutralizing antibodies, nanobodies, and other affinity proteins against SARS-CoV-2 and related viruses to address current and future pandemics. While isolating antibodies from animals and humans are proven approaches, these methods are limited to the affinities, specificities, and functional activities of antibodies generated by the immune system. Here we report a surprisingly simple directed evolution method for generating nanobodies with high affinities and neutralization activities against SARS-CoV-2. We demonstrate that complementarity-determining region swapping between low-affinity lead nanobodies, which we discovered unintentionally but find is simple to implement systematically, results in matured nanobodies with unusually large increases in affinity. Importantly, the matured nanobodies potently neutralize both SARS-CoV-2 pseudovirus and live virus, and possess drug-like biophysical properties. We expect that our methods will improve in vitro nanobody discovery and accelerate the generation of potent neutralizing nanobodies against diverse coronaviruses.
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