Evidence map›Paper›PMID 31510934›Full record

ArticleBMC infectious diseases2019

Inhibition of replication of hepatitis B virus using transcriptional repressors that target the viral DNA.

Kristie Bloom, Haajira Kaldine, Toni Cathomen, Claudio Mussolino, Abdullah Ely, Patrick Arbuthnot

Open access · goldAbstract read
In one paragraph

Article in BMC infectious diseases, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing 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

12 citing papers in PubMed, 27 citations in OpenAlex.

  1. Epigenome editing based treatment: Progresses and challenges.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
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  5. The role of HBV cccDNA in occult hepatitis B virus infection.Molecular and cellular biochemistry · 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

6 authors at 2 institutions in 2 countries.

Kristie BloomWits/SAMRC Antiviral Gene Therapy Research Unit, School of Pathology, Faculty of Health Science, University of the Witwatersrand, Private Bag 3, WITS, Johannesburg, 2050, South Africa.
Haajira KaldineWits/SAMRC Antiviral Gene Therapy Research Unit, School of Pathology, Faculty of Health Science, University of the Witwatersrand, Private Bag 3, WITS, Johannesburg, 2050, South Africa.
Toni CathomenInstitute for Transfusion Medicine and Gene Therapy, Medical Center - University of Freiburg, Freiburg, Germany.
Claudio MussolinoInstitute for Transfusion Medicine and Gene Therapy, Medical Center - University of Freiburg, Freiburg, Germany.
Abdullah ElyWits/SAMRC Antiviral Gene Therapy Research Unit, School of Pathology, Faculty of Health Science, University of the Witwatersrand, Private Bag 3, WITS, Johannesburg, 2050, South Africa.
Patrick ArbuthnotWits/SAMRC Antiviral Gene Therapy Research Unit, School of Pathology, Faculty of Health Science, University of the Witwatersrand, Private Bag 3, WITS, Johannesburg, 2050, South Africa. Patrick.Arbuthnot@wits.ac.za.ORCID http://orcid.org/0000-0003-4149-8995
South African Medical Research Council · ZAUniversity of Freiburg · DE

Funding

German Federal Ministry for Education and Research HBVTALE-10DG15005, BMBF-01EO0803South African National Research Foundation 81768, 81692, 68339, 85981 & 77954South African Poliomyelitis Research Foundation Not applicable
6 · The paper itself

Abstract

backgroundChronic infection with hepatitis B virus (HBV) is a serious global health problem. Persistence of the virus occurs as a result of stability of the replication intermediate comprising covalently closed circular DNA (cccDNA). Development of drugs that are capable of disabling this cccDNA is vital.

methodsTo investigate an epigenetic approach to inactivating viral DNA, we engineered transcriptional repressors that comprise an HBV DNA-binding domain of transcription activator like effectors (TALEs) and a fused Krüppel Associated Box (KRAB). These repressor TALEs (rTALEs) targeted the viral surface open reading frame and were placed under transcription control of constitutively active or liver-specific promoters.

resultsEvaluation in cultured cells and following hydrodynamic injection of mice revealed that the rTALEs significantly inhibited production of markers of HBV replication without evidence of hepatotoxicity. Increased methylation of HBV DNA at CpG island II showed that the rTALEs caused intended epigenetic modification.

conclusionsEpigenetic modification of HBV DNA is a new and effective means of inactivating the virus in vivo. The approach has therapeutic potential and avoids potentially problematic unintended mutagenesis of gene editing.

Indexed as

AnimalsCell LineCpG IslandsDNA, CircularDNA MethylationDNA, ViralEpigenesis, GeneticFemaleHepatitis BHepatitis B virusLiverMiceOpen Reading FramesPromoter Regions, GeneticRepressor ProteinsVirus ReplicationDNA, CircularDNA, ViralRepressor ProteinsDNA methylationHBVKRABTALETranscriptional repressor

Identifiers

PMID31510934
PMCPMC6739920
OpenAlexW2972640160

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.