Evidence map›Paper›PMID 31107136›Full record

ArticlemAbs2019

A comprehensive search of functional sequence space using large mammalian display libraries created by gene editing.

Kothai Parthiban, Rajika L Perera, Maheen Sattar, Yanchao Huang, Sophie Mayle, Edward Masters, Daniel Griffiths, Sachin Surade, Rachael Leah, Michael R Dyson and 1 more

Open access · goldAbstract read
In one paragraph

Article in mAbs, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
2.1field-weighted citation impact, top 12% 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

37 citing papers in PubMed, 56 citations in OpenAlex.

  1. Article
  2. Review
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  6. Multiplex, multimodal mapping of variant effects in secreted proteins.bioRxiv : the preprint server for biology · 2025
    Article
  7. Review
  8. Review
  9. Review
  10. Fluorescence-activated droplet sequencing (FAD-seq) directly provides sequences of screening hits in antibody discovery.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  11. Article
  12. Review
  13. Article
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  15. Article
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  19. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Kothai Parthibana IONTAS Ltd , Cambridge , UK.
Rajika L Pereraa IONTAS Ltd , Cambridge , UK.ORCID 0000-0002-4932-8168
Maheen Sattara IONTAS Ltd , Cambridge , UK.
Yanchao Huanga IONTAS Ltd , Cambridge , UK.
Sophie Maylea IONTAS Ltd , Cambridge , UK.ORCID 0000-0001-9913-7995
Edward Mastersa IONTAS Ltd , Cambridge , UK.
Daniel Griffithsa IONTAS Ltd , Cambridge , UK.ORCID 0000-0003-2938-3570
Sachin Suradea IONTAS Ltd , Cambridge , UK.ORCID 0000-0002-8545-8867
Rachael Leaha IONTAS Ltd , Cambridge , UK.
Michael R Dysona IONTAS Ltd , Cambridge , UK.ORCID 0000-0002-8382-0789
John McCaffertya IONTAS Ltd , Cambridge , UK.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The construction of large libraries in mammalian cells allows the direct screening of millions of molecular variants for binding properties in a cell type relevant for screening or production. We have created mammalian cell libraries of up to 10 million clones displaying a repertoire of IgG-formatted antibodies on the cell surface. TALE nucleases or CRISPR/Cas9 were used to direct the integration of the antibody genes into a single genomic locus, thereby rapidly achieving stable expression and transcriptional normalization. The utility of the system is illustrated by the affinity maturation of a PD-1-blocking antibody through the systematic mutation and functional survey of 4-mer variants within a 16 amino acid paratope region. Mutating VH CDR3 only, we identified a dominant "solution" involving substitution of a central tyrosine to histidine. This appears to be a local affinity maximum, and this variant was surpassed by a lysine substitution when light chain variants were introduced. We achieve this comprehensive and quantitative interrogation of sequence space by combining high-throughput oligonucleotide synthesis with mammalian display and flow cytometry operating at the multi-million scale.

Indexed as

Antibody AffinityAnimalsAntibodies, Monoclonal, HumanizedBinding Sites, AntibodyCHO CellsComplementarity Determining RegionsCricetulusCRISPR-Cas SystemsEndodeoxyribonucleasesFlow CytometryGene EditingHEK293 CellsHumansImmunoglobulin Heavy ChainsMutagenesis, Site-DirectedProgrammed Cell Death 1 ReceptorAntibodies, Monoclonal, HumanizedComplementarity Determining RegionsEndodeoxyribonucleasesImmunoglobulin Heavy ChainsProgrammed Cell Death 1 Receptoraffinity maturationCRISPR/Cas9fluorescence-activated cell sortinggene editinggene targetinghuman therapeutic antibody discoveryIgG antibody librarymagnetic-activated cell sortingMammalian displayTALE nuclease

Identifiers

PMID31107136
PMCPMC6601556
OpenAlexW2944979862

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

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.