Evidence map›Paper›PMID 27746349›Full record

ArticleNeuroscience2016

C3 transferase gene therapy for continuous conditional RhoA inhibition.

Claire-Anne Gutekunst, Jack K Tung, Margaret E McDougal, Robert E Gross

Abstract readValidation Study
In one paragraph

Article in Neuroscience, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed, 1 pooled it
0.5field-weighted citation impact, top 34% 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

12 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.

  1. Pooled it
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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

4 authors at 3 institutions in 1 country.

Claire-Anne GutekunstDepartment of Neurosurgery, Emory University School of Medicine, Atlanta, GA, United States. Electronic address: cguteku@emory.edu.
Jack K TungDepartment of Neurosurgery, Emory University School of Medicine, Atlanta, GA, United States; Wallace H. Coulter Department of Biomedical Engineering, Emory University School of Medicine and Georgia Institute of Technology College of Engineering, Atlanta, GA, United States. Electronic address: jtung@emory.edu.
Margaret E McDougalDepartment of Neurosurgery, Emory University School of Medicine, Atlanta, GA, United States. Electronic address: mmcdoug@emory.edu.
Robert E GrossDepartment of Neurosurgery, Emory University School of Medicine, Atlanta, GA, United States; Department of Neurology, Emory University School of Medicine, Atlanta, GA, United States; Wallace H. Coulter Department of Biomedical Engineering, Emory University School of Medicine and Georgia Institute of Technology College of Engineering, Atlanta, GA, United States. Electronic address: rgross@emory.edu.
Emory University · USGeorgia Institute of Technology · USThe Wallace H. Coulter Department of Biomedical Engineering · US

Funding

Atlanta Clinical and Translational Science Institute (ACTSI) RenewalUL1TR000454 · NCATS · EMORY UNIVERSITY · PI STEPHENS, DAVID S · 2012 to 2016
$25.8M
ENNCF - Viral Vector CoreP30NS055077 · NINDS · EMORY UNIVERSITY · PI LEVEY, ALLAN I · 2008 to 2018
$6.8M
Optogenetic Population Clamp to Study Long-term Plasticity in VitroR01NS079757 · NINDS · GEORGIA INSTITUTE OF TECHNOLOGY · PI BUTERA, ROBERT J · 2012 to 2016
$1.5M
C3 transferase Gene Therapy for CNS Axon RegenerationR03NS091699 · NINDS · EMORY UNIVERSITY · PI GROSS, ROBERT E · 2015 to 2016
$156k
NCATS NIH HHS UL1 TR000454NINDS NIH HHS P30 NS055077NINDS NIH HHS R01 NS079757NINDS NIH HHS R03 NS091699
6 · The paper itself

Abstract

Regrowth inhibitory molecules prevent axon regeneration in the adult mammalian central nervous system (CNS). RhoA, a small GTPase in the Rho family, is a key intracellular switch that mediates the effects of these extracellular regrowth inhibitors. The bacterial enzyme C3-ADP ribosyltransferase (C3) selectively and irreversibly inhibits the activation of RhoA and stimulates axon outgrowth and regeneration. However, effective intracellular delivery of the C3 protein in vivo is limited by poor cell permeability and a short duration of action. To address this, we have developed a gene therapy approach using viral vectors to introduce the C3 gene into neurons or neuronal progenitors. Our vectors deliver C3 in a cell-autonomous (endogenous) or a cell-nonautonomous (secretable/permeable) fashion and promote in vitro process outgrowth on inhibitory chondroitin sulfate proteoglycan substrate. Further conditional control of our vectors was achieved via the addition of a Tet-On system, which allows for transcriptional control with doxycycline administration. These vectors will be crucial tools for promoting continued axonal regeneration after CNS injuries or neurodegenerative diseases.

Indexed as

Genetic TherapyNeuronal OutgrowthADP Ribose TransferasesAnimalsAxonsBotulinum ToxinsCerebral CortexChondroitin Sulfate ProteoglycansCorpus StriatumDependovirusDoxycyclineGenetic VectorsHEK293 CellsHumansLentivirusMaleADP Ribose TransferasesBotulinum ToxinsChondroitin Sulfate ProteoglycansDoxycyclineexoenzyme C3, Clostridium botulinumrhoA GTP-Binding Proteinaxonal regenerationC3 transferasecentral nervous systemgene therapyRhoA inhibition

Identifiers

PMID27746349
PMCPMC5118153
OpenAlexW2530010317

What OpenQuestion holds

Textmetadata
LicenceTDM
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.