Evidence map›Paper›PMID 31953402›Full record

ArticleNature communications2020

An ultra-stable cytoplasmic antibody engineered for in vivo applications.

Hiroyuki Kabayama, Makoto Takeuchi, Naoko Tokushige, Shin-Ichi Muramatsu, Miyuki Kabayama, Mitsunori Fukuda, Yoshiyuki Yamada, Katsuhiko Mikoshiba

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
2.4field-weighted citation impact, top 9% 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

20 citing papers in PubMed, 37 citations in OpenAlex.

  1. Article
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  6. Conformation-specific synthetic intrabodies modulate mTOR signaling with subcellular spatial resolution.Proceedings of the National Academy of Sciences of the United States of America · 2025
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  17. Reporter gene systems: A powerful tool forCurrent research in microbial sciences · 2022
    Article
  18. Review
  19. Applying Antibodies Inside Cells: Principles and Recent Advances in Neurobiology, Virology and Oncology.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2020
    Review
  20. New Insights Into Drug Discovery Targeting Tau Protein.Frontiers in molecular neuroscience · 2020
    Review
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

8 authors at 5 institutions in 2 countries.

Hiroyuki KabayamaLaboratory for Developmental Neurobiology, Center for Brain Science, Institute of Physical and Chemical Research, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan. D19002@nvlu.ac.jp.ORCID http://orcid.org/0000-0002-5482-1950
Makoto TakeuchiLaboratory for Developmental Neurobiology, Center for Brain Science, Institute of Physical and Chemical Research, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan.
Naoko TokushigeLaboratory for Developmental Neurobiology, Center for Brain Science, Institute of Physical and Chemical Research, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan.
Shin-Ichi MuramatsuDivision of Neurological Gene Therapy, Center for Open Innovation, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan.ORCID http://orcid.org/0000-0002-3185-7790
Miyuki KabayamaDivision of Functional Morphology, Department of Basic Veterinary Medicine, School of Veterinary Medicine, Nippon Veterinary and Life Science University, 1-7-1 Kyonantyo, Musashino, Tokyo, 180-8602, Japan.
Mitsunori FukudaLaboratory of Membrane Trafficking Mechanisms, Department of Integrative Life Sciences, Graduate School of Life Sciences, Tohoku University, Aobayama, Aoba-ku, Sendai, Miyagi, 980-8578, Japan.ORCID http://orcid.org/0000-0002-8620-5853
Yoshiyuki YamadaLaboratory for Developmental Neurobiology, Center for Brain Science, Institute of Physical and Chemical Research, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan.
Katsuhiko MikoshibaLaboratory for Developmental Neurobiology, Center for Brain Science, Institute of Physical and Chemical Research, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan. mikosiba@shanghaitech.edu.cn.
RIKEN Center for Brain Science · JPNippon Veterinary and Life Science University · JPJichi Medical University · JPTohoku University · JPToho University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Targeting cytoplasmic protein-protein interactions with antibodies remains technically challenging, since antibodies expressed in the cytosol frequently form insoluble aggregates. Existing engineering methods are based on the notion that the estimated net charge at pH 7.4 affects stability; as such, they are unable to overcome this problem. Herein, we report a versatile method for engineering an ultra-stable cytoplasmic antibody (STAND), with a strong estimated net negative charge at pH 6.6, by fusing peptide tags with a highly negative charge and a low isoelectric point. Without the need for complicated amino acid substitutions, we convert aggregation-prone antibodies to STANDs that are useful for inhibiting in vivo transmitter release, modulating animal behaviour, and inhibiting in vivo cancer proliferation driven by mutated Kras-long recognised as an "undruggable" oncogenic protein. The STAND method shows promise for targeting endogenous cytoplasmic proteins in basic biology and for developing future disease treatments.

Indexed as

Amino Acid SequenceAmino Acid SubstitutionAnimalsAntibodiesBehavior, AnimalCell ProliferationChlorocebus aethiopsCOS CellsCytoplasmHEK293 CellsHeLa CellsHumansHydrogen-Ion ConcentrationMaleMiceNeoplasmsAntibodies

Identifiers

PMID31953402
PMCPMC6969036
OpenAlexW2999633004

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.