Evidence map›Paper›PMID 25968319›Full record

ArticleDevelopment (Cambridge, England)2015

Enhanced selective gene delivery to neural stem cells in vivo by an adeno-associated viral variant.

Melissa A Kotterman, Tandis Vazin, David V Schaffer

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Development (Cambridge, England), 2015. 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
2.5field-weighted citation impact, top 10% 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, 34 citations in OpenAlex.

  1. Review
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  10. Article
  11. AAV diffuses across zona pellucida for effortless gene delivery to fertilized eggs.Biochemical and biophysical research communications · 2020
    Article
  12. Article
  13. Recombinant Viral Vectors as Neuroscience Tools.Current protocols in neuroscience · 2019
    Review
  14. Article
  15. Review
  16. Review
  17. Article
  18. Article
  19. Review
  20. Article
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

3 authors at 1 institution in 1 country.

Melissa A KottermanDepartment of Chemical and Biomolecular Engineering, University of California, Berkeley, CA 94720, USA Department of Bioengineering, University of California, Berkeley, CA 94720, USA The Helen Wills Neuroscience Institute, University of California, Berkeley, CA 94720, USA 4D Molecular Therapeutics, San Francisco, CA 94107, USA.
Tandis VazinDepartment of Chemical and Biomolecular Engineering, University of California, Berkeley, CA 94720, USA Department of Bioengineering, University of California, Berkeley, CA 94720, USA The Helen Wills Neuroscience Institute, University of California, Berkeley, CA 94720, USA.
David V SchafferDepartment of Chemical and Biomolecular Engineering, University of California, Berkeley, CA 94720, USA Department of Bioengineering, University of California, Berkeley, CA 94720, USA The Helen Wills Neuroscience Institute, University of California, Berkeley, CA 94720, USA 4D Molecular Therapeutics, San Francisco, CA 94107, USA Department of Molecular and Cellular Biology, University of California, Berkeley, CA 94720-1462, USA schaffer@berkeley.edu.
University of California, Berkeley · US

Funding

Mechanisms of Neural Stem Cell MechanoregulationR01NS074831 · NINDS · UNIVERSITY OF CALIFORNIA BERKELEY · PI Sanjay Kumar, DAVID V SCHAFFER · 2012 to 2026
$5.9M
NINDS NIH HHS R01 NS074831
6 · The paper itself

Abstract

Neural stem cells (NSCs) are defined by their ability to self-renew and to differentiate into mature neuronal and glial cell types. NSCs are the subject of intense investigation, owing to their crucial roles in neural development and adult brain function and because they present potential targets for gene and cell replacement therapies following injury or disease. Approaches to specifically genetically perturb or modulate NSC function would be valuable for either motivation. Unfortunately, most gene delivery vectors are incapable of efficient or specific gene delivery to NSCs in vivo. Vectors based on adeno-associated virus (AAV) present a number of advantages and have proven increasingly successful in clinical trials. However, natural AAV variants are inefficient in transducing NSCs. We previously engineered a novel AAV variant (AAV r3.45) capable of efficient transduction of adult NSCs in vitro. Here, to build upon the initial promise of this variant, we investigated its in vitro and in vivo infectivity. AAV r3.45 was more selective for NSCs than mature neurons in a human embryonic stem cell-derived culture containing a mixture of cell types, including NSCs and neurons. It was capable of more efficient and selective transduction of rat and mouse NSCs in vivo than natural AAV serotypes following intracranial vector administration. Delivery of constitutively active β-catenin yielded insights into mechanisms by which this key regulator modulates NSC function, indicating that this engineered AAV variant can be harnessed for preferential modulation of adult NSCs in the hippocampus. The capacity to rapidly genetically modify these cells might greatly accelerate in vivo investigations of adult neurogenesis.

Indexed as

Animalsbeta CateninCell LineDependovirusGene Transfer TechniquesHumansMiceNeural Stem CellsRatsbeta CateninAdeno-associated virusGene deliveryNeural stem cell

Identifiers

PMID25968319
PMCPMC4440921
OpenAlexW2170890844

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.