Evidence map›Paper›PMID 37973910›Full record

ArticleNature communications2023

A toolbox of astrocyte-specific, serotype-independent adeno-associated viral vectors using microRNA targeting sequences.

Amy J Gleichman, Riki Kawaguchi, Michael V Sofroniew, S Thomas Carmichael

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 50 papers.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed
9.0field-weighted citation impact, top 2% 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

50 citing papers in PubMed, 55 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

4 authors at 1 institution in 1 country.

Amy J GleichmanDepartment of Neurology, David Geffen School of Medicine at University of California-Los Angeles, Los Angeles, CA, USA.ORCID 0000-0003-1029-4471
Riki KawaguchiCenter for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA, USA.
Michael V SofroniewDepartment of Neurobiology, University of California-Los Angeles, Los Angeles, CA, USA.ORCID 0000-0001-6075-0178
S Thomas CarmichaelDepartment of Neurology, David Geffen School of Medicine at University of California-Los Angeles, Los Angeles, CA, USA. SCarmichael@mednet.ucla.edu.ORCID 0000-0002-1169-9203
University of California, Los Angeles · US

Funding

UCLA IDDRC: Translational CoreP50HD103557 · NICHD · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI SUSAN Y BOOKHEIMER · 2020 to 2026
$9.6M
NICHD NIH HHS P50 HD103557
6 · The paper itself

Abstract

Astrocytes, one of the most prevalent cell types in the central nervous system (CNS), are critically involved in neural function. Genetically manipulating astrocytes is an essential tool in understanding and affecting their roles. Adeno-associated viruses (AAVs) enable rapid genetic manipulation; however, astrocyte specificity of AAVs can be limited, with high off-target expression in neurons and sparsely in endothelial cells. Here, we report the development of a cassette of four copies of six miRNA targeting sequences (4x6T) which triggers transgene degradation specifically in neurons and endothelial cells. In combination with the GfaABC1D promoter, 4x6T increases astrocytic specificity of Cre with a viral reporter from <50% to >99% in multiple serotypes in mice, and confers astrocyte specificity in multiple recombinases and reporters. We also present empty vectors to add 4x6T to other cargo, independently and in Cre/Dre-dependent forms. This toolbox of AAVs allows rapid manipulation of astrocytes throughout the CNS, is compatible with different AAV serotypes, and demonstrates the efficacy of using multiplexed miRNA targeting sequences to decrease expression in multiple off-target cell populations simultaneously.

Indexed as

AstrocytesMicroRNAsAnimalsDependovirusEndothelial CellsGenetic VectorsMiceSerogroupMicroRNAs

Identifiers

PMID37973910
PMCPMC10654773
OpenAlexW4388720746

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.