Evidence map›Paper›PMID 29931269›Full record

ArticleNucleic acids research2018

High-throughput antibody engineering in mammalian cells by CRISPR/Cas9-mediated homology-directed mutagenesis.

Derek M Mason, Cédric R Weber, Cristina Parola, Simon M Meng, Victor Greiff, William J Kelton, Sai T Reddy

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
4.1field-weighted citation impact, top 5% 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

42 citing papers in PubMed, 83 citations in OpenAlex.

  1. Review
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  3. A Synthetic Platform for Antibody Junctional Diversification Beyond Natural Constraints.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
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  12. Multiplex, multimodal mapping of variant effects in secreted proteins.bioRxiv : the preprint server for biology · 2025
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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

7 authors at 2 institutions in 1 country.

Derek M MasonDepartment of Biosystems Science and Engineering, ETH Zürich, Basel 4058, Switzerland.
Cédric R WeberDepartment of Biosystems Science and Engineering, ETH Zürich, Basel 4058, Switzerland.
Cristina ParolaDepartment of Biosystems Science and Engineering, ETH Zürich, Basel 4058, Switzerland.
Simon M MengDepartment of Biosystems Science and Engineering, ETH Zürich, Basel 4058, Switzerland.
Victor GreiffDepartment of Biosystems Science and Engineering, ETH Zürich, Basel 4058, Switzerland.
William J KeltonDepartment of Biosystems Science and Engineering, ETH Zürich, Basel 4058, Switzerland.
Sai T ReddyDepartment of Biosystems Science and Engineering, ETH Zürich, Basel 4058, Switzerland.
ETH Zurich · CHUniversity of Zurich · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Antibody engineering is often performed to improve therapeutic properties by directed evolution, usually by high-throughput screening of phage or yeast display libraries. Engineering antibodies in mammalian cells offer advantages associated with expression in their final therapeutic format (full-length glycosylated IgG); however, the inability to express large and diverse libraries severely limits their potential throughput. To address this limitation, we have developed homology-directed mutagenesis (HDM), a novel method which extends the concept of CRISPR/Cas9-mediated homology-directed repair (HDR). HDM leverages oligonucleotides with degenerate codons to generate site-directed mutagenesis libraries in mammalian cells. By improving HDR to a robust efficiency of 15-35% and combining mammalian display screening with next-generation sequencing, we validated this approach can be used for key applications in antibody engineering at high-throughput: rational library construction, novel variant discovery, affinity maturation and deep mutational scanning (DMS). We anticipate that HDM will be a valuable tool for engineering and optimizing antibodies in mammalian cells, and eventually enable directed evolution of other complex proteins and cellular therapeutics.

Indexed as

CRISPR-Cas SystemsMutagenesis, Site-DirectedAmino Acid SequenceAnimalsAntibodiesAntibody AffinityBase SequenceCell LineDNA Breaks, Double-StrandedHigh-Throughput Nucleotide SequencingHumansHybridomasOligonucleotidesProtein EngineeringRecombinational DNA RepairAntibodiesOligonucleotides

Identifiers

PMID29931269
PMCPMC6101513
OpenAlexW2789710996

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.