Evidence map›Paper›PMID 30195763›Full record

ArticleMolecular therapy. Nucleic acids2018

One-Vector System for Multiplexed CRISPR/Cas9 against Hepatitis B Virus cccDNA Utilizing High-Capacity Adenoviral Vectors.

Maren Schiwon, Eric Ehrke-Schulz, Andreas Oswald, Thorsten Bergmann, Thomas Michler, Ulrike Protzer, Anja Ehrhardt

Open access · goldAbstract read
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 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
3.2field-weighted citation impact, top 7% 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

44 citing papers in PubMed, 72 citations in OpenAlex.

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  11. CRISPR/Cas9 systems: Delivery technologies and biomedical applications.Asian journal of pharmaceutical sciences · 2023
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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 4 institutions in 1 country.

Maren SchiwonCenter of Biomedical Education and Research (ZBAF), Department of Human Medicine, Faculty of Health, Witten/Herdecke University, Witten, Germany.
Eric Ehrke-SchulzCenter of Biomedical Education and Research (ZBAF), Department of Human Medicine, Faculty of Health, Witten/Herdecke University, Witten, Germany.
Andreas OswaldInstitute of Virology, Technical University of Munich/Helmholtz Zentrum München, Munich, Germany.
Thorsten BergmannCenter of Biomedical Education and Research (ZBAF), Department of Human Medicine, Faculty of Health, Witten/Herdecke University, Witten, Germany.
Thomas MichlerInstitute of Virology, Technical University of Munich/Helmholtz Zentrum München, Munich, Germany; German Center for Infection Research (DZIF), partner site Munich, Munich, Germany.
Ulrike ProtzerInstitute of Virology, Technical University of Munich/Helmholtz Zentrum München, Munich, Germany; German Center for Infection Research (DZIF), partner site Munich, Munich, Germany.
Anja EhrhardtCenter of Biomedical Education and Research (ZBAF), Department of Human Medicine, Faculty of Health, Witten/Herdecke University, Witten, Germany. Electronic address: anja.ehrhardt@uni-wh.de.
Witten/Herdecke University · DEGerman Center for Infection Research · DEHelmholtz Zentrum München · DETechnical University of Munich · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

High-capacity adenoviral vectors (HCAdVs) devoid of all coding genes are powerful tools to deliver large DNA cargos into cells. Here HCAdVs were designed to deliver a multiplexed complete CRISPR/Cas9 nuclease system or a complete pair of transcription activator-like effector nucleases (TALENs) directed against the hepatitis B virus (HBV) genome. HBV, which remains a serious global health burden, forms covalently closed circular DNA (cccDNA) as a persistent DNA species in infected cells. This cccDNA promotes the chronic carrier status, and it represents a major hurdle in the treatment of chronic HBV infection. To date, only one study demonstrated viral delivery of a CRISPR/Cas9 system and a single guide RNA (gRNA) directed against HBV by adeno-associated viral (AAV) vectors. The advancement of this study is the co-delivery of multiple gRNA expression cassettes along with the Cas9 expression cassette in one HCAdV. Treatment of HBV infection models resulted in a significant reduction of HBV antigen production and the introduction of mutations into the HBV genome. In the transduction experiments, the HBV genome, including the HBV cccDNA, was degraded by the CRISPR/Cas9 system. In contrast, the combination of two parts of a TALEN pair in one vector could not be proven to yield an active system. In conclusion, we successfully delivered the CRISPR/Cas9 system containing three gRNAs using HCAdV, and we demonstrated its antiviral effect.

Indexed as

cccDNA degradationchronic HBV infectionhigh-capacity adenovirusmultiplexed CRISPR/Cas9

Identifiers

PMID30195763
PMCPMC6023846
OpenAlexW2806638145

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.