Rapid generation of potent antibodies by autonomous hypermutation in yeast.
Nat Chem Biol
; 17(10): 1057-1064, 2021 10.
Article
in English
| MEDLINE | ID: covidwho-1281726
ABSTRACT
The predominant approach for antibody generation remains animal immunization, which can yield exceptionally selective and potent antibody clones owing to the powerful evolutionary process of somatic hypermutation. However, animal immunization is inherently slow, not always accessible and poorly compatible with many antigens. Here, we describe 'autonomous hypermutation yeast surface display' (AHEAD), a synthetic recombinant antibody generation technology that imitates somatic hypermutation inside engineered yeast. By encoding antibody fragments on an error-prone orthogonal DNA replication system, surface-displayed antibody repertoires continuously mutate through simple cycles of yeast culturing and enrichment for antigen binding to produce high-affinity clones in as little as two weeks. We applied AHEAD to generate potent nanobodies against the SARS-CoV-2 S glycoprotein, a G-protein-coupled receptor and other targets, offering a template for streamlined antibody generation at large.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Recombinant Proteins
/
Protein Engineering
/
Antibody Formation
Type of study:
Randomized controlled trials
Limits:
Humans
Language:
English
Journal:
Nat Chem Biol
Journal subject:
Biology
/
Chemistry
Year:
2021
Document Type:
Article
Affiliation country:
S41589-021-00832-4
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