Evidence map›Paper›PMID 32576975›Full record

ArticleGene therapy2021

Optimization of adeno-associated viral vector-mediated transduction of the corticospinal tract: comparison of four promoters.

Bart Nieuwenhuis, Barbara Haenzi, Sam Hilton, Alejandro Carnicer-Lombarte, Barbara Hobo, Joost Verhaagen, James W Fawcett

Open access · hybridAbstract read
In one paragraph

Article in Gene therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
74citing papers in PubMed, 2 pooled it
12.6field-weighted citation impact, top 1% 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

74 citing papers in PubMed, 2 syntheses or guidelines pooled it, 108 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Erasable serum markers.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  11. Review
  12. Article
  13. Article
  14. Developing a minimally invasive gene therapy for multiple sclerosis.Molecular therapy. Methods & clinical development · 2025
    Article
  15. Article
  16. Review
  17. Combining Machine Learning and Multiplexed,bioRxiv : the preprint server for biology · 2025
    Article
  18. Article
  19. Current trends in gene therapy to treat inherited disorders of the brain.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
  20. AAV vector development, back to the future.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review

14 more citing papers are in PubMed but not listed here.

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

7 authors at 3 institutions in 3 countries.

Bart NieuwenhuisJohn van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Forvie Site, Robinson Way, Cambridge, CB2 0PY, UK. bn246@cam.ac.uk.ORCID http://orcid.org/0000-0002-2065-2271
Barbara HaenziJohn van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Forvie Site, Robinson Way, Cambridge, CB2 0PY, UK.ORCID http://orcid.org/0000-0001-5144-534X
Sam HiltonJohn van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Forvie Site, Robinson Way, Cambridge, CB2 0PY, UK.ORCID http://orcid.org/0000-0003-3938-6046
Alejandro Carnicer-LombarteJohn van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Forvie Site, Robinson Way, Cambridge, CB2 0PY, UK.ORCID https://orcid.org/0000-0002-5650-4692
Barbara HoboLaboratory for Regeneration of Sensorimotor Systems, Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences (KNAW), Meibergdreef 47, 1105 BA, Amsterdam, The Netherlands.
Joost VerhaagenLaboratory for Regeneration of Sensorimotor Systems, Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences (KNAW), Meibergdreef 47, 1105 BA, Amsterdam, The Netherlands.ORCID http://orcid.org/0000-0002-8341-1096
James W FawcettJohn van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Forvie Site, Robinson Way, Cambridge, CB2 0PY, UK.ORCID http://orcid.org/0000-0002-7990-4568
University of Cambridge · GBNetherlands Institute for Neuroscience · NLRoyal Netherlands Academy of Arts and Sciences · NL

Funding

Medical Research Council MR/R004463/1Medical Research Council MR/R004544/1Medical Research Council MR/V002694/1
6 · The paper itself

Abstract

Adeno-associated viral vectors are widely used as vehicles for gene transfer to the nervous system. The promoter and viral vector serotype are two key factors that determine the expression dynamics of the transgene. A previous comparative study has demonstrated that AAV1 displays efficient transduction of layer V corticospinal neurons, but the optimal promoter for transgene expression in corticospinal neurons has not been determined yet. In this paper, we report a side-by-side comparison between four commonly used promoters: the short CMV early enhancer/chicken β actin (sCAG), human cytomegalovirus (hCMV), mouse phosphoglycerate kinase (mPGK) and human synapsin (hSYN) promoter. Reporter constructs with each of these promoters were packaged in AAV1, and were injected in the sensorimotor cortex of rats and mice in order to transduce the corticospinal tract. Transgene expression levels and the cellular transduction profile were examined after 6 weeks. The AAV1 vectors harbouring the hCMV and sCAG promoters resulted in transgene expression in neurons, astrocytes and oligodendrocytes. The mPGK and hSYN promoters directed the strongest transgene expression. The mPGK promoter did drive expression in cortical neurons and oligodendrocytes, while transduction with AAV harbouring the hSYN promoter resulted in neuron-specific expression, including perineuronal net expressing interneurons and layer V corticospinal neurons. This promoter comparison study contributes to improve transgene delivery into the brain and spinal cord. The optimized transduction of the corticospinal tract will be beneficial for spinal cord injury research.

Indexed as

DependovirusPyramidal TractsAnimalsGenetic VectorsMicePromoter Regions, GeneticRatsTransduction, GeneticTransgenes

Identifiers

PMID32576975
PMCPMC7902269
OpenAlexW3035790625

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.