Evidence map›Paper›PMID 40872804›Full record

ArticleViruses2025

Lipid Nanoparticle-Encapsulated TALEN-Encoding mRNA Inactivates Hepatitis B Virus Replication in Cultured Cells and Transgenic Mice.

Tiffany Smith, Prashika Singh, Ridhwaanah Bhana, Dylan Kairuz, Kristie Bloom, Mohube Betty Maepa, Abdullah Ely, Patrick Arbuthnot

Abstract read
In one paragraph

Article in Viruses, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

8 authors.

Tiffany SmithWits/SAMRC Antiviral Gene Therapy Research Unit, Infectious Diseases and Oncology Research Institute (IDORI), School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Parktown 2193, South Africa.
Prashika SinghWits/SAMRC Antiviral Gene Therapy Research Unit, Infectious Diseases and Oncology Research Institute (IDORI), School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Parktown 2193, South Africa.
Ridhwaanah BhanaWits/SAMRC Antiviral Gene Therapy Research Unit, Infectious Diseases and Oncology Research Institute (IDORI), School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Parktown 2193, South Africa.
Dylan KairuzWits/SAMRC Antiviral Gene Therapy Research Unit, Infectious Diseases and Oncology Research Institute (IDORI), School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Parktown 2193, South Africa.
Kristie BloomWits/SAMRC Antiviral Gene Therapy Research Unit, Infectious Diseases and Oncology Research Institute (IDORI), School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Parktown 2193, South Africa.ORCID 0000-0001-5796-7720
Mohube Betty MaepaWits/SAMRC Antiviral Gene Therapy Research Unit, Infectious Diseases and Oncology Research Institute (IDORI), School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Parktown 2193, South Africa.ORCID 0000-0002-2249-7615
Abdullah ElyWits/SAMRC Antiviral Gene Therapy Research Unit, Infectious Diseases and Oncology Research Institute (IDORI), School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Parktown 2193, South Africa.ORCID 0000-0002-1205-2436
Patrick ArbuthnotWits/SAMRC Antiviral Gene Therapy Research Unit, Infectious Diseases and Oncology Research Institute (IDORI), School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Parktown 2193, South Africa.ORCID 0000-0003-4149-8995

Funding

Poliomyelitis Research Foundation Postgraduate bursarySouth African Medial Research Council Extramural Resarch UnitSouth African National Research Council 118022 and 120383
6 · The paper itself

Abstract

Chronic infection with the hepatitis B virus (HBV) results in over 1 million deaths annually. Although currently licensed treatments, including pegylated interferon-α and nucleoside/nucleotide analogs, can inhibit viral replication, they rarely eradicate covalently closed circular DNA (cccDNA) reservoirs. Moreover, vaccination does not offer therapeutic benefit to already infected individuals or non-responders. Consequently, chronic infection is maintained by the persistence of cccDNA in infected hepatocytes. For this reason, novel therapeutic strategies that permanently inactivate cccDNA are a priority. Obligate heterodimeric transcription activator-like effector nucleases (TALENs) provide the precise gene-editing needed to disable cccDNA. To develop this strategy using a therapeutically relevant approach, TALEN-encoding mRNA targeting viral core and surface genes was synthesized using in vitro transcription with co-transcriptional capping. TALENs reduced hepatitis B surface antigen (HBsAg) by 80% in a liver-derived mammalian cell culture model of infection. In a stringent HBV transgenic murine model, a single dose of hepatotropic lipid nanoparticle-encapsulated TALEN mRNA lowered HBsAg by 63% and reduced viral particle equivalents by more than 99%, without evidence of toxicity. A surveyor assay demonstrated mean in vivo HBV DNA mutation rates of approximately 16% and 15% for Core and Surface TALENs, respectively. This study presents the first evidence of the therapeutic potential of TALEN-encoding mRNA to inactivate HBV replication permanently.

Indexed as

Hepatitis B virusNanoparticlesRNA, MessengerTranscription Activator-Like Effector NucleasesVirus ReplicationAnimalsAntiviral AgentsDisease Models, AnimalDNA, CircularHepatitis BHepatitis B Surface AntigensHepatocytesHumansLipidsLiposomesMiceAntiviral AgentsDNA, CircularHepatitis B Surface AntigensLipid NanoparticlesLipidsLiposomesRNA, MessengerTranscription Activator-Like Effector NucleasescccDNAcoreHBsAgHBVLNPTALEN mRNA

Identifiers

PMID40872804
PMCPMC12390527

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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.