Evidence map›Paper›PMID 26482836›Full record

ArticleScientific reports2015

Combinatorial RNA Interference Therapy Prevents Selection of Pre-existing HBV Variants in Human Liver Chimeric Mice.

Yao-Ming Shih, Cheng-Pu Sun, Hui-Hsien Chou, Tzu-Hui Wu, Chun-Chi Chen, Ping-Yi Wu, Yu-Chen Enya Chen, Karl-Dimiter Bissig, Mi-Hua Tao

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
2.0field-weighted citation impact, top 13% 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

9 citing papers in PubMed, 21 citations in OpenAlex.

  1. Targeting HBV with RNA interference: Paths to cure.Science translational medicine · 2025
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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

9 authors at 5 institutions in 3 countries.

Yao-Ming ShihGraduate Institute of Microbiology, National Taiwan University, Taipei, Taiwan.
Cheng-Pu SunInstitute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
Hui-Hsien ChouDepartment of Computer Science, Iowa State University, Ames, Iowa, United States of America.
Tzu-Hui WuDepartment of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University, Taipei, Taiwan.
Chun-Chi ChenCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
Ping-Yi WuInstitute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
Yu-Chen Enya ChenInstitute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
Karl-Dimiter BissigDepartment of Molecular and Cellular Biology, Center for Cell and Gene Therapy, Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, One Baylor Plaza, BCM505, Alkek Building, N1010.07, Houston, TX 77030, USA.
Mi-Hua TaoGraduate Institute of Microbiology, National Taiwan University, Taipei, Taiwan.
Institute of Biomedical Sciences, Academia Sinica · TWNational Taiwan University · TWBaylor College of Medicine · USInstitute of Microbiology · CNIowa State University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Selection of escape mutants with mutations within the target sequence could abolish the antiviral RNA interference activity. Here, we investigated the impact of a pre-existing shRNA-resistant HBV variant on the efficacy of shRNA therapy. We previously identified a highly potent shRNA, S1, which, when delivered by an adeno-associated viral vector, effectively inhibits HBV replication in HBV transgenic mice. We applied the "PICKY" software to systemically screen the HBV genome, then used hydrodynamic transfection and HBV transgenic mice to identify additional six highly potent shRNAs. Human liver chimeric mice were infected with a mixture of wild-type and T472C HBV, a S1-resistant HBV variant, and then treated with a single or combined shRNAs. The presence of T472C mutant compromised the therapeutic efficacy of S1 and resulted in replacement of serum wild-type HBV by T472C HBV. In contrast, combinatorial therapy using S1 and P28, one of six potent shRNAs, markedly reduced titers for both wild-type and T472C HBV. Interestingly, treatment with P28 alone led to the emergence of escape mutants with mutations in the P28 target region. Our results demonstrate that combinatorial RNAi therapy can minimize the escape of resistant viral mutants in chronic HBV patients.

Indexed as

Genetic TherapyGenetic VariationRNA InterferenceAnimalsComputational BiologyDependovirusDisease Models, AnimalDNA, CircularDNA, ComplementaryDNA, ViralGenetic VectorsHepatitis B, ChronicHepatitis B virusHumansLiver TransplantationMiceDNA, CircularDNA, ComplementaryDNA, ViralRNA, Small InterferingRNA, Viral

Identifiers

PMID26482836
PMCPMC4612501
OpenAlexW2334983393

What OpenQuestion holds

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LicenceCC BY
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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.