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Rapid generation of potent antibodies by autonomous hypermutation in yeast.
Wellner, Alon; McMahon, Conor; Gilman, Morgan S A; Clements, Jonathan R; Clark, Sarah; Nguyen, Kianna M; Ho, Ming H; Hu, Vincent J; Shin, Jung-Eun; Feldman, Jared; Hauser, Blake M; Caradonna, Timothy M; Wingler, Laura M; Schmidt, Aaron G; Marks, Debora S; Abraham, Jonathan; Kruse, Andrew C; Liu, Chang C.
  • Wellner A; Department of Biomedical Engineering, University of California, Irvine, CA, USA.
  • McMahon C; Department of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
  • Gilman MSA; Vertex Pharmaceuticals, Boston, MA, USA.
  • Clements JR; Department of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
  • Clark S; Department of Biomedical Engineering, University of California, Irvine, CA, USA.
  • Nguyen KM; Department of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
  • Ho MH; Department of Biomedical Engineering, University of California, Irvine, CA, USA.
  • Hu VJ; Department of Biomedical Engineering, University of California, Irvine, CA, USA.
  • Shin JE; Department of Biomedical Engineering, University of California, Irvine, CA, USA.
  • Feldman J; Department of Systems Biology, Harvard Medical School, Boston, MA, USA.
  • Hauser BM; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
  • Caradonna TM; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
  • Wingler LM; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
  • Schmidt AG; Department of Medicine, Duke University Medical Center, Durham, NC, USA.
  • Marks DS; Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC, USA.
  • Abraham J; Department of Pharmacology and Cancer Biology, Duke University, Durham, NC, USA.
  • Kruse AC; Department of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
  • Liu CC; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
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.
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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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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