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Rapid generation of potent antibodies by autonomous hypermutation in yeast.

Publication ,  Journal Article
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 ...
Published in: Nat Chem Biol
October 2021

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.

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Published In

Nat Chem Biol

DOI

EISSN

1552-4469

Publication Date

October 2021

Volume

17

Issue

10

Start / End Page

1057 / 1064

Location

United States

Related Subject Headings

  • Spike Glycoprotein, Coronavirus
  • Single-Domain Antibodies
  • Saccharomyces cerevisiae
  • SARS-CoV-2
  • Recombinant Proteins
  • Protein Engineering
  • Peptide Library
  • Humans
  • COVID-19
  • Biochemistry & Molecular Biology
 

Citation

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Wellner, A., McMahon, C., Gilman, M. S. A., Clements, J. R., Clark, S., Nguyen, K. M., … Liu, C. C. (2021). Rapid generation of potent antibodies by autonomous hypermutation in yeast. Nat Chem Biol, 17(10), 1057–1064. https://doi.org/10.1038/s41589-021-00832-4
Wellner, Alon, Conor McMahon, Morgan S. A. Gilman, Jonathan R. Clements, Sarah Clark, Kianna M. Nguyen, Ming H. Ho, et al. “Rapid generation of potent antibodies by autonomous hypermutation in yeast.Nat Chem Biol 17, no. 10 (October 2021): 1057–64. https://doi.org/10.1038/s41589-021-00832-4.
Wellner A, McMahon C, Gilman MSA, Clements JR, Clark S, Nguyen KM, et al. Rapid generation of potent antibodies by autonomous hypermutation in yeast. Nat Chem Biol. 2021 Oct;17(10):1057–64.
Wellner, Alon, et al. “Rapid generation of potent antibodies by autonomous hypermutation in yeast.Nat Chem Biol, vol. 17, no. 10, Oct. 2021, pp. 1057–64. Pubmed, doi:10.1038/s41589-021-00832-4.
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. Rapid generation of potent antibodies by autonomous hypermutation in yeast. Nat Chem Biol. 2021 Oct;17(10):1057–1064.

Published In

Nat Chem Biol

DOI

EISSN

1552-4469

Publication Date

October 2021

Volume

17

Issue

10

Start / End Page

1057 / 1064

Location

United States

Related Subject Headings

  • Spike Glycoprotein, Coronavirus
  • Single-Domain Antibodies
  • Saccharomyces cerevisiae
  • SARS-CoV-2
  • Recombinant Proteins
  • Protein Engineering
  • Peptide Library
  • Humans
  • COVID-19
  • Biochemistry & Molecular Biology