Evidence map›Paper›PMID 30982889›Full record

ArticleNucleic acids research2019

Cell-specific CRISPR-Cas9 activation by microRNA-dependent expression of anti-CRISPR proteins.

Mareike D Hoffmann, Sabine Aschenbrenner, Stefanie Grosse, Kleopatra Rapti, Claire Domenger, Julia Fakhiri, Manuel Mastel, Kathleen Börner, Roland Eils, Dirk Grimm and 1 more

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.

0numbers the graph read from it
0cells of the map it votes in
70citing papers in PubMed
5.7field-weighted citation impact, top 3% 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

70 citing papers in PubMed, 114 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Review
  6. Methods to Quantify the MicroRNA and Study Their Role in Genotoxic Stress.Methods in molecular biology (Clifton, N.J.) · 2026
    Article
  7. Review
  8. Article
  9. Article
  10. Protective antigen-mediated delivery of an anti-CRISPR protein for precision genome editing.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  11. Article
  12. Mechanism of Cas9 inhibition by AcrIIA11.Nucleic acids research · 2025
    Article
  13. Review
  14. Article
  15. Review
  16. Review
  17. Article
  18. Article
  19. Article
  20. Review

10 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

11 authors at 5 institutions in 1 country.

Mareike D HoffmannSynthetic Biology Group, Institute for Pharmacy and Biotechnology (IPMB) and Center for Quantitative Analysis of Molecular and Cellular Biosystems (BioQuant), University of Heidelberg, Heidelberg 69120, Germany.
Sabine AschenbrennerSynthetic Biology Group, Institute for Pharmacy and Biotechnology (IPMB) and Center for Quantitative Analysis of Molecular and Cellular Biosystems (BioQuant), University of Heidelberg, Heidelberg 69120, Germany.
Stefanie GrosseSynthetic Biology Group, Institute for Pharmacy and Biotechnology (IPMB) and Center for Quantitative Analysis of Molecular and Cellular Biosystems (BioQuant), University of Heidelberg, Heidelberg 69120, Germany.
Kleopatra RaptiDepartment of Infectious Diseases, Virology, University Hospital Heidelberg, Heidelberg 69120, Germany.
Claire DomengerDepartment of Infectious Diseases, Virology, University Hospital Heidelberg, Heidelberg 69120, Germany.
Julia FakhiriDepartment of Infectious Diseases, Virology, University Hospital Heidelberg, Heidelberg 69120, Germany.
Manuel MastelSynthetic Biology Group, Institute for Pharmacy and Biotechnology (IPMB) and Center for Quantitative Analysis of Molecular and Cellular Biosystems (BioQuant), University of Heidelberg, Heidelberg 69120, Germany.
Kathleen BörnerDepartment of Infectious Diseases, Virology, University Hospital Heidelberg, Heidelberg 69120, Germany.
Roland EilsDigital Health Center, Berlin Institute of Health (BIH) and Charité, Berlin 10178, Germany.
Dirk GrimmDepartment of Infectious Diseases, Virology, University Hospital Heidelberg, Heidelberg 69120, Germany.
Dominik NiopekSynthetic Biology Group, Institute for Pharmacy and Biotechnology (IPMB) and Center for Quantitative Analysis of Molecular and Cellular Biosystems (BioQuant), University of Heidelberg, Heidelberg 69120, Germany.
Heidelberg University · DEUniversity Hospital Heidelberg · DEBerlin Institute of Health at Charité - Universitätsmedizin Berlin · DEGerman Cancer Research Center · DEGerman Center for Infection Research · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The rapid development of CRISPR-Cas technologies brought a personalized and targeted treatment of genetic disorders into closer reach. To render CRISPR-based therapies precise and safe, strategies to confine the activity of Cas(9) to selected cells and tissues are highly desired. Here, we developed a cell type-specific Cas-ON switch based on miRNA-regulated expression of anti-CRISPR (Acr) proteins. We inserted target sites for miR-122 or miR-1, which are abundant specifically in liver and cardiac muscle cells, respectively, into the 3'UTR of Acr transgenes. Co-expressing these with Cas9 and sgRNAs resulted in Acr knockdown and released Cas9 activity solely in hepatocytes or cardiomyocytes, while Cas9 was efficiently inhibited in off-target cells. We demonstrate control of genome editing and gene activation using a miR-dependent AcrIIA4 in combination with different Streptococcus pyogenes (Spy)Cas9 variants (full-length Cas9, split-Cas9, dCas9-VP64). Finally, to showcase its modularity, we adapted our Cas-ON system to the smaller and more target-specific Neisseria meningitidis (Nme)Cas9 orthologue and its cognate inhibitors AcrIIC1 and AcrIIC3. Our Cas-ON switch should facilitate cell-specific activity of any CRISPR-Cas orthologue, for which a potent anti-CRISPR protein is known.

Indexed as

CRISPR-Cas SystemsGene Expression RegulationTransgenes3' Untranslated RegionsBinding SitesCRISPR-Associated Protein 9DependovirusEnzyme ActivationEnzyme InductionGene EditingGenes, ReporterHEK293 CellsHeLa CellsHepatocytesHumansLuciferases, Renilla3' Untranslated RegionsCas9 endonuclease Streptococcus pyogenesCRISPR-Associated Protein 9Luciferases, RenillaMicroRNAsMIRN122 microRNA, humanMIRN1 microRNA, humanProtein Isoforms

Identifiers

PMID30982889
PMCPMC6648350
OpenAlexW2953362829

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.