Evidence map›Paper›PMID 24011174›Full record

ArticleBioconjugate chemistry2013

Synthetic self-assembling clostridial chimera for modulation of sensory functions.

Enrico Ferrari, Chunjing Gu, Dhevahi Niranjan, Laura Restani, Christine Rasetti-Escargueil, Ilona Obara, Sandrine M Geranton, Jason Arsenault, Tom A Goetze, Callista B Harper and 12 more

Open access · hybridAbstract read
In one paragraph

Article in Bioconjugate chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
2.7field-weighted citation impact, top 11% 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

15 citing papers in PubMed, 35 citations in OpenAlex.

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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

22 authors at 9 institutions in 3 countries.

Enrico FerrariMRC Laboratory of Molecular Biology , Cambridge, United Kingdom.
Chunjing Gu
Dhevahi Niranjan
Laura Restani
Christine Rasetti-Escargueil
Ilona Obara
Sandrine M Geranton
Jason Arsenault
Tom A Goetze
Callista B Harper
Tam H Nguyen
Elizabeth Maywood
John O'Brien
Giampietro Schiavo
Daniel W Wheeler
Frederic A Meunier
Michael Hastings
J Michael Edwardson
Dorothea Sesardic
Matteo Caleo
Stephen P Hunt
Bazbek Davletov
MRC Laboratory of Molecular Biology · GBUniversity College London · GBUniversity of Queensland · AUIstituto di Scienza e Tecnologie dell'Informazione "Alessandro Faedo" · ITNational Institute for Biological Standards and Control · GBUniversity of Cambridge · GBAddenbrooke's Hospital · GBCancer Research UK · GBUniversity of Lincoln · GB

Funding

Medical Research Council G1100577Medical Research Council MC_U105170643Medical Research Council MC_U105178791Medical Research Council MR/K022539/1Medical Research Council U10578791Wellcome TrustWellcome Trust 089125/Z/09/Z
6 · The paper itself

Abstract

Clostridial neurotoxins reversibly block neuronal communication for weeks and months. While these proteolytic neurotoxins hold great promise for clinical applications and the investigation of brain function, their paralytic activity at neuromuscular junctions is a stumbling block. To redirect the clostridial activity to neuronal populations other than motor neurons, we used a new self-assembling method to combine the botulinum type A protease with the tetanus binding domain, which natively targets central neurons. The two parts were produced separately and then assembled in a site-specific way using a newly introduced 'protein stapling' technology. Atomic force microscopy imaging revealed dumbbell shaped particles which measure ∼23 nm. The stapled chimera inhibited mechanical hypersensitivity in a rat model of inflammatory pain without causing either flaccid or spastic paralysis. Moreover, the synthetic clostridial molecule was able to block neuronal activity in a defined area of visual cortex. Overall, we provide the first evidence that the protein stapling technology allows assembly of distinct proteins yielding new biomedical properties.

Indexed as

AnimalsBotulinum Toxins, Type ABrainCells, CulturedClostridium botulinumClostridium tetaniMaleMiceMice, Inbred BALB CMice, Inbred C57BLModels, MolecularNeuronsPain ThresholdRatsRecombinant Fusion ProteinsTetanus ToxinBotulinum Toxins, Type ARecombinant Fusion ProteinsTetanus Toxin

Identifiers

PMID24011174
PMCPMC3901392
OpenAlexW2006453007

What OpenQuestion holds

Textmetadata
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.