Evidence map›Paper›PMID 29499926›Full record

ArticleMolecular therapy. Nucleic acids2018

RNA Nanotherapeutics for the Amelioration of Astroglial Reactivity.

Jayden A Smith, Alice Braga, Jeroen Verheyen, Silvia Basilico, Sara Bandiera, Clara Alfaro-Cervello, Luca Peruzzotti-Jametti, Dan Shu, Farzin Haque, Peixuan Guo and 1 more

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

Article in Molecular therapy. Nucleic acids, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.0field-weighted citation impact, top 24% 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

13 citing papers in PubMed, 22 citations in OpenAlex.

  1. Review
  2. Review
  3. Astrocyte involvement in metabolic regulation and disease.Trends in endocrinology and metabolism: TEM · 2025
    Review
  4. Article
  5. Article
  6. Review
  7. Review
  8. Article
  9. Combination of In Situ Lcn2 pRNA-RNAi Nanotherapeutics and iNSC Transplantation Ameliorates Experimental SCI in Mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2020
    Article
  10. Therapeutic siRNA: state of the art.Signal transduction and targeted therapy · 2020
    Review
  11. Article
  12. Review
  13. 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

11 authors at 4 institutions in 3 countries.

Jayden A SmithDepartment of Clinical Neurosciences, Division of Stem Cell Neurobiology, Wellcome Trust-Medical Research Council Stem Cell Institute and NIHR Biomedical Research Centre, University of Cambridge, Cambridge, UK. Electronic address: jayden.smith@citc-ltd.co.uk.
Alice BragaDepartment of Clinical Neurosciences, Division of Stem Cell Neurobiology, Wellcome Trust-Medical Research Council Stem Cell Institute and NIHR Biomedical Research Centre, University of Cambridge, Cambridge, UK; Department of Diagnostics and Public Health, University of Verona, Verona 37134, Italy.
Jeroen VerheyenDepartment of Clinical Neurosciences, Division of Stem Cell Neurobiology, Wellcome Trust-Medical Research Council Stem Cell Institute and NIHR Biomedical Research Centre, University of Cambridge, Cambridge, UK.
Silvia BasilicoDepartment of Clinical Neurosciences, Division of Stem Cell Neurobiology, Wellcome Trust-Medical Research Council Stem Cell Institute and NIHR Biomedical Research Centre, University of Cambridge, Cambridge, UK.
Sara BandieraDepartment of Clinical Neurosciences, Division of Stem Cell Neurobiology, Wellcome Trust-Medical Research Council Stem Cell Institute and NIHR Biomedical Research Centre, University of Cambridge, Cambridge, UK; Department of Life Sciences, University of Trieste, Trieste 34127, Italy.
Clara Alfaro-CervelloDepartment of Clinical Neurosciences, Division of Stem Cell Neurobiology, Wellcome Trust-Medical Research Council Stem Cell Institute and NIHR Biomedical Research Centre, University of Cambridge, Cambridge, UK.
Luca Peruzzotti-JamettiDepartment of Clinical Neurosciences, Division of Stem Cell Neurobiology, Wellcome Trust-Medical Research Council Stem Cell Institute and NIHR Biomedical Research Centre, University of Cambridge, Cambridge, UK.
Dan ShuCollege of Pharmacy, Division of Pharmaceutics and Pharmaceutical Chemistry, The Ohio State University, Columbus, OH, USA; College of Medicine, Department of Physiology and Cell Biology, The Ohio State University, Columbus, OH, USA; Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, USA; NCI Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA; Center for RNA Nanobiotechnology and Nanomedicine, The Ohio State University, Columbus, OH, USA.
Farzin HaqueCollege of Pharmacy, Division of Pharmaceutics and Pharmaceutical Chemistry, The Ohio State University, Columbus, OH, USA; College of Medicine, Department of Physiology and Cell Biology, The Ohio State University, Columbus, OH, USA; Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, USA; NCI Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA; Center for RNA Nanobiotechnology and Nanomedicine, The Ohio State University, Columbus, OH, USA.
Peixuan GuoCollege of Pharmacy, Division of Pharmaceutics and Pharmaceutical Chemistry, The Ohio State University, Columbus, OH, USA; College of Medicine, Department of Physiology and Cell Biology, The Ohio State University, Columbus, OH, USA; Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, USA; NCI Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA; Center for RNA Nanobiotechnology and Nanomedicine, The Ohio State University, Columbus, OH, USA. Electronic address: guo.1091@osu.edu.
Stefano PluchinoDepartment of Clinical Neurosciences, Division of Stem Cell Neurobiology, Wellcome Trust-Medical Research Council Stem Cell Institute and NIHR Biomedical Research Centre, University of Cambridge, Cambridge, UK. Electronic address: spp24@cam.ac.uk.
Wellcome/MRC Cambridge Stem Cell Institute · GBLung Institute · USUniversity of Trieste · ITUniversity of Verona · IT

Funding

European Research Council 260511Wellcome Trust
6 · The paper itself

Abstract

In response to injuries to the CNS, astrocytes enter a reactive state known as astrogliosis, which is believed to be deleterious in some contexts. Activated astrocytes overexpress intermediate filaments including glial fibrillary acidic protein (GFAP) and vimentin (Vim), resulting in entangled cells that inhibit neurite growth and functional recovery. Reactive astrocytes also secrete inflammatory molecules such as Lipocalin 2 (Lcn2), which perpetuate reactivity and adversely affect other cells of the CNS. Herein, we report proof-of-concept use of the packaging RNA (pRNA)-derived three-way junction (3WJ) motif as a platform for the delivery of siRNAs to downregulate such reactivity-associated genes. In vitro, siRNA-3WJs induced a significant knockdown of Gfap, Vim, and Lcn2 in a model of astroglial activation, with a concomitant reduction in protein expression. Knockdown of Lcn2 also led to reduced protein secretion from reactive astroglial cells, significantly impeding the perpetuation of inflammation in otherwise quiescent astrocytes. Intralesional injection of anti-Lcn2-3WJs in mice with contusion spinal cord injury led to knockdown of Lcn2 at mRNA and protein levels in vivo. Our results provide evidence for siRNA-3WJs as a promising platform for ameliorating astroglial reactivity, with significant potential for further functionalization and adaptation for therapeutic applications in the CNS.

Indexed as

astrocytesastrogliosisLipocalin2neuroinflammationpRNARNA nanotherapeuticssiRNAspinal cord injury

Identifiers

PMID29499926
PMCPMC5738063
OpenAlexW2770436052

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.