Evidence map›Paper›PMID 37853101›Full record

ArticleScientific reports2023

Inactive S. aureus Cas9 downregulates alpha-synuclein and reduces mtDNA damage and oxidative stress levels in human stem cell model of Parkinson's disease.

Danuta Sastre, Faria Zafar, C Alejandra Morato Torres, Desiree Piper, Deniz Kirik, Laurie H Sanders, L Stanley Qi, Birgitt Schüle

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

Article in Scientific reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
2.2field-weighted citation impact, top 12% 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

16 citing papers in PubMed, 14 citations in OpenAlex.

  1. Review
  2. Advances and clinical potential of epigenome editing.Cellular and molecular life sciences : CMLS · 2026
    Review
  3. CRISPR-Based Gene Therapy for Brain Disease.Molecular neurobiology · 2026
    Review
  4. Review
  5. Rab12 is a regulator of mitophagy and mitochondrial homeostasis.bioRxiv : the preprint server for biology · 2026
    Article
  6. Article
  7. Review
  8. Review
  9. Review
  10. Review
  11. Article
  12. Review
  13. Review
  14. Article
  15. A short guide on blue fluorescent proteins: limits and perspectives.Applied microbiology and biotechnology · 2024
    Review
  16. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 5 institutions in 2 countries.

Danuta Sastre *Department of Pathology, Stanford University School of Medicine, 300 Pasteur Dr., R271/217, Stanford, CA, 94305, USA.
Faria Zafar *Department of Pathology, Stanford University School of Medicine, 300 Pasteur Dr., R271/217, Stanford, CA, 94305, USA.
C Alejandra Morato TorresDepartment of Pathology, Stanford University School of Medicine, 300 Pasteur Dr., R271/217, Stanford, CA, 94305, USA.
Desiree PiperDepartment of Biological Sciences, San Jose State University, San Jose, CA, 95192, USA.
Deniz KirikDepartment of Experimental Medical Science, Lund University, Lund, Sweden.
Laurie H SandersDepartments of Neurology and Pathology, Duke Center for Neurodegeneration and Neurotherapeutics, Duke University Medical Center, Durham, NC, 27710, USA.
L Stanley QiDepartment of Bioengineering, Stanford University, Stanford, CA, 94305, USA.
Birgitt SchüleDepartment of Pathology, Stanford University School of Medicine, 300 Pasteur Dr., R271/217, Stanford, CA, 94305, USA. bschuele@stanford.edu.
Stanford University · USDuke University Hospital · USLund University · SESan Jose State University · USSRI International · US

Funding

Mechanisms of mitochondrial genome integrity in familial and idiopathic Parkinson's diseaseR01NS119528 · NINDS · DUKE UNIVERSITY · PI SANDERS, LAURIE H · 2020 to 2024
$2.9M
NINDS NIH HHS R01 NS119528
6 · The paper itself

Abstract

Parkinson's disease (PD) is one of the most common neurodegenerative diseases, but no disease modifying therapies have been successful in clinical translation presenting a major unmet medical need. A promising target is alpha-synuclein or its aggregated form, which accumulates in the brain of PD patients as Lewy bodies. While it is not entirely clear which alpha-synuclein protein species is disease relevant, mere overexpression of alpha-synuclein in hereditary forms leads to neurodegeneration. To specifically address gene regulation of alpha-synuclein, we developed a CRISPR interference (CRISPRi) system based on the nuclease dead S. aureus Cas9 (SadCas9) fused with the transcriptional repressor domain Krueppel-associated box to controllably repress alpha-synuclein expression at the transcriptional level. We screened single guide (sg)RNAs across the SNCA promoter and identified several sgRNAs that mediate downregulation of alpha-synuclein at varying levels. CRISPRi downregulation of alpha-synuclein in iPSC-derived neuronal cultures from a patient with an SNCA genomic triplication showed functional recovery by reduction of oxidative stress and mitochondrial DNA damage. Our results are proof-of-concept in vitro for precision medicine by targeting the SNCA gene promoter. The SNCA CRISPRi approach presents a new model to understand safe levels of alpha-synuclein downregulation and a novel therapeutic strategy for PD and related alpha-synucleinopathies.

Indexed as

Methicillin-Resistant Staphylococcus aureusParkinson Diseasealpha-SynucleinCRISPR-Cas SystemsDNA, MitochondrialHumansOxidative StressRNA, Guide, CRISPR-Cas SystemsStaphylococcus aureusStem Cellsalpha-SynucleinDNA, MitochondrialRNA, Guide, CRISPR-Cas Systems

Identifiers

PMID37853101
PMCPMC10584834
OpenAlexW4387730281

What OpenQuestion holds

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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.