Rapid generation of potent antibodies by autonomous hypermutation in yeast.

Journal Article (Journal Article)

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

Duke Authors

Cited Authors

  • Wellner, A; McMahon, C; Gilman, MSA; Clements, JR; Clark, S; Nguyen, KM; Ho, MH; Hu, VJ; Shin, J-E; Feldman, J; Hauser, BM; Caradonna, TM; Wingler, LM; Schmidt, AG; Marks, DS; Abraham, J; Kruse, AC; Liu, CC

Published Date

  • October 2021

Published In

Volume / Issue

  • 17 / 10

Start / End Page

  • 1057 - 1064

PubMed ID

  • 34168368

Pubmed Central ID

  • PMC8463502

Electronic International Standard Serial Number (EISSN)

  • 1552-4469

Digital Object Identifier (DOI)

  • 10.1038/s41589-021-00832-4

Language

  • eng

Conference Location

  • United States