Evidence map›Paper›PMID 34168368›Full record

ArticleNature chemical biology2021

Rapid generation of potent antibodies by autonomous hypermutation in yeast.

Alon Wellner, Conor McMahon, Morgan S A Gilman, Jonathan R Clements, Sarah Clark, Kianna M Nguyen, Ming H Ho, Vincent J Hu, Jung-Eun Shin, Jared Feldman and 8 more

Open access · bronzeAbstract read
In one paragraph

Article in Nature chemical biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
78citing papers in PubMed, 1 pooled it
12.2field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

78 citing papers in PubMed, 1 synthesis or guideline pooled it, 127 citations in OpenAlex.

  1. Pooled it
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  12. Yeast-mediated display: probingIranian journal of microbiology · 2025
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18 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors at 5 institutions in 1 country.

Alon Wellner *Department of Biomedical Engineering, University of California, Irvine, CA, USA.
Conor McMahon *Department of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Morgan S A GilmanDepartment of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Jonathan R ClementsDepartment of Biomedical Engineering, University of California, Irvine, CA, USA.
Sarah ClarkDepartment of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0001-9944-0919
Kianna M NguyenDepartment of Biomedical Engineering, University of California, Irvine, CA, USA.
Ming H HoDepartment of Biomedical Engineering, University of California, Irvine, CA, USA.
Vincent J HuDepartment of Biomedical Engineering, University of California, Irvine, CA, USA.ORCID http://orcid.org/0000-0001-8580-067X
Jung-Eun ShinDepartment of Systems Biology, Harvard Medical School, Boston, MA, USA.
Jared FeldmanRagon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
Blake M HauserRagon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
Timothy M CaradonnaRagon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-7138-4441
Laura M WinglerDepartment of Medicine, Duke University Medical Center, Durham, NC, USA.ORCID http://orcid.org/0000-0002-3688-5088
Aaron G SchmidtDepartment of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0003-3627-2553
Debora S MarksDepartment of Systems Biology, Harvard Medical School, Boston, MA, USA.
Jonathan AbrahamDepartment of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Andrew C KruseDepartment of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA. andrew_kruse@hms.harvard.edu.ORCID http://orcid.org/0000-0002-1467-1222
Chang C LiuDepartment of Biomedical Engineering, University of California, Irvine, CA, USA. ccl@uci.edu.ORCID http://orcid.org/0000-0002-3290-2880
Harvard University · USUniversity of California, Irvine · USRagon Institute of MGH, MIT and Harvard · USBroad Institute · USHoward Hughes Medical Institute · US

Funding

Medical Scientist Training ProgramT32GM007753 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WALENSKY, LOREN DAVID · 1985 to 2021
$50.0M
MOLECULAR BIOPHYSICS TRAINING GRANTT32GM008313 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI MURTHY, VENKATESH N · 1989 to 2023
$14.6M
MOLECULAR BASIS OF VIRAL INFECTIVITYT32AI007245 · NIAID · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI Aaron Gregory Schmidt · 1985 to 2026
$11.3M
Making antibody generation rapid, scalable, and democratic through machine learning and continuous evolutionR01CA260415 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI KRUSE, ANDREW, LIU, CHANG C · 2020 to 2024
$8.4M
Epitope focusing to the receptor binding motif for a universal coronavirus vaccineR01AI146779 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI SCHMIDT, AARON GREGORY · 2019 to 2023
$4.2M
Diversity Supplement for A High-Throughput Continuous Evolution System for in vivo Biosensor EngineeringDP2GM119163 · NIGMS · UNIVERSITY OF CALIFORNIA-IRVINE · PI LIU, CHANG C · 2015 to 2017
$2.5M
Synthetic genetic systems for rapid biomolecular evolution in vivoR35GM136297 · NIGMS · UNIVERSITY OF CALIFORNIA-IRVINE · PI LIU, CHANG C · 2020 to 2024
$2.4M
Molecular mechanisms of adiponectin signaling and PAQR functionDP5OD021345 · OD · HARVARD MEDICAL SCHOOL · PI KRUSE, ANDREW · 2015 to 2019
$2.1M
Gordon and Betty Moore Foundation (Gordon E. and Betty I. Moore Foundation) Inventors FellowshipNCI NIH HHS R01 CA260415NIAID NIH HHS R01 AI146779NIAID NIH HHS T32 AI007245NIGMS NIH HHS DP2 GM119163NIGMS NIH HHS R35 GM136297NIGMS NIH HHS T32 GM007753NIGMS NIH HHS T32 GM008313NIH HHS DP5 OD021345UC | University of California, Irvine (UC Irvine) COVID-19 Basic, Translational and Clinical Research FundU.S. Department of Health & Human Services | National Institutes of Health (NIH) 1R01CA260415U.S. Department of Health & Human Services | National Institutes of Health (NIH) 1R35GM136297U.S. Department of Health & Human Services | National Institutes of Health (NIH) DP5OD021345U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01AI146779U.S. Department of Health & Human Services | National Institutes of Health (NIH) T32GM007753Vallee Foundation (Bert L. & N. Kuggie Vallee Foundation) Scholars Award
6 · The paper itself

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.

Indexed as

AntibodiesAntibody FormationAntigensCOVID-19HumansPeptide LibraryProtein EngineeringRecombinant ProteinsSaccharomyces cerevisiaeSARS-CoV-2Single-Domain AntibodiesSpike Glycoprotein, CoronavirusAntibodiesAntigensPeptide LibraryRecombinant ProteinsSingle-Domain AntibodiesSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2

Identifiers

PMID34168368
PMCPMC8463502
OpenAlexW3176264499

What OpenQuestion holds

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LicenceTDM
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.