Evidence map›Paper›PMID 36997531›Full record

ArticleNature communications2023

A Vaccinia-based system for directed evolution of GPCRs in mammalian cells.

Christoph Klenk, Maria Scrivens, Anina Niederer, Shuying Shi, Loretta Mueller, Elaine Gersz, Maurice Zauderer, Ernest S Smith, Ralf Strohner, Andreas Plückthun

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.2field-weighted citation impact, top 21% 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

6 citing papers in PubMed, 8 citations in OpenAlex.

  1. Anti-CRISPR-mediated continuous directed evolution of CRISPR-Cas9 in human cells.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  2. Journal of the American Chemical Society · 2026
    Article
  3. Article
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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

10 authors at 4 institutions in 3 countries.

Christoph KlenkDepartment of Biochemistry, University of Zurich, Winterthurerstrasse 190, CH-8057, Zurich, Switzerland. c.klenk@bioc.uzh.ch.ORCID 0000-0001-5199-7144
Maria ScrivensVaccinex, Inc., 1895 Mt. Hope Avenue, Rochester, New York, 14620, NY, USA.
Anina NiedererDepartment of Biochemistry, University of Zurich, Winterthurerstrasse 190, CH-8057, Zurich, Switzerland.ORCID 0000-0002-1124-4030
Shuying ShiVaccinex, Inc., 1895 Mt. Hope Avenue, Rochester, New York, 14620, NY, USA.
Loretta MuellerVaccinex, Inc., 1895 Mt. Hope Avenue, Rochester, New York, 14620, NY, USA.
Elaine GerszVaccinex, Inc., 1895 Mt. Hope Avenue, Rochester, New York, 14620, NY, USA.ORCID 0009-0008-5384-7084
Maurice ZaudererVaccinex, Inc., 1895 Mt. Hope Avenue, Rochester, New York, 14620, NY, USA.ORCID 0000-0002-4253-9165
Ernest S SmithVaccinex, Inc., 1895 Mt. Hope Avenue, Rochester, New York, 14620, NY, USA.
Ralf StrohnerMorphoSys AG, Semmelweisstr. 7, 82152, Planegg, Germany.
Andreas PlückthunDepartment of Biochemistry, University of Zurich, Winterthurerstrasse 190, CH-8057, Zurich, Switzerland. plueckthun@bioc.uzh.ch.ORCID 0000-0003-4191-5306
Vaccinex (United States) · USZHAW Zurich University of Applied Sciences · CHMorphoSys (Germany) · DEUniversity of Zurich · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Directed evolution in bacterial or yeast display systems has been successfully used to improve stability and expression of G protein-coupled receptors for structural and biophysical studies. Yet, several receptors cannot be tackled in microbial systems due to their complex molecular composition or unfavorable ligand properties. Here, we report an approach to evolve G protein-coupled receptors in mammalian cells. To achieve clonality and uniform expression, we develop a viral transduction system based on Vaccinia virus. By rational design of synthetic DNA libraries, we first evolve neurotensin receptor 1 for high stability and expression. Second, we demonstrate that receptors with complex molecular architectures and large ligands, such as the parathyroid hormone 1 receptor, can be readily evolved. Importantly, functional receptor properties can now be evolved in the presence of the mammalian signaling environment, resulting in receptor variants exhibiting increased allosteric coupling between the ligand binding site and the G protein interface. Our approach thus provides insights into the intricate molecular interplay required for GPCR activation.

Indexed as

VacciniaAnimalsLigandsMammalsReceptors, G-Protein-CoupledSignal TransductionVaccinia virusLigandsReceptors, G-Protein-Coupled

Identifiers

PMID36997531
PMCPMC10063554
OpenAlexW4361273492

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.