ArticleMolecular therapy. Nucleic acids2014
In vitro Inactivation of Latent HSV by Targeted Mutagenesis Using an HSV-specific Homing Endonuclease.
Article in Molecular therapy. Nucleic acids, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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.
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.
Who cites it
34 citing papers in PubMed, 50 citations in OpenAlex.
- CRISPR-Cas9-mediated genome editing delivered by a single AAV9 vector inhibits HSV-1 reactivation in a latent rabbit keratitis model.Molecular therapy. Methods & clinical development · 2024Article
- Suppression of HSV-1 infection and viral reactivation by CRISPR-Cas9 gene editing in 2D and 3D culture models.Molecular therapy. Nucleic acids · 2024Article
- Summary of the Centers for Disease Control and Prevention/National Institute of Allergy and Infectious Diseases Joint Workshop on Genital Herpes: 3-4 November 2022.Open forum infectious diseases · 2024Review
- HSV-1 exploits host heterochromatin for nuclear egress.The Journal of cell biology · 2023Article
- Longitudinal Detection of Twenty DNA and RNA Viruses in Allogeneic Hematopoietic Stem Cell Transplant Recipients Plasma.Viruses · 2023Observational
- Current landscape in antiviral drug development against herpes simplex virus infections.Smart medicine · 2022Review
- Article
- CRISPR-Cas9 Expressed in Stably Transduced Cell Lines Promotes Recombination and Selects for Herpes Simplex Virus Recombinants.Current research in virological science · 2022Article
- CRISPR-Cas9 gene editing of hepatitis B virus in chronically infected humanized mice.Molecular therapy. Methods & clinical development · 2021Article
- Review
- Single AAV-Mediated CRISPR-SaCas9 Inhibits HSV-1 Replication by Editing ICP4 in Trigeminal Ganglion Neurons.Molecular therapy. Methods & clinical development · 2020Article
- Gene editing and elimination of latent herpes simplex virus in vivo.Nature communications · 2020Article
- Biologic interactions between HSV-2 and HIV-1 and possible implications for HSV vaccine development.Vaccine · 2019Review
- CRISPR/Cas9 and Genome Editing for Viral Disease-Is Resistance Futile?ACS infectious diseases · 2018Review
- Applications of Alternative Nucleases in the Age of CRISPR/Cas9.International journal of molecular sciences · 2017Review
- Double deficiency of Trex2 and DNase1L2 nucleases leads to accumulation of DNA in lingual cornifying keratinocytes without activating inflammatory responses.Scientific reports · 2017Article
- In vivo dynamics of AAV-mediated gene delivery to sensory neurons of the trigeminal ganglia.Scientific reports · 2017Article
- Disruption or Excision of Provirus as an Approach to HIV Cure.AIDS patient care and STDs · 2016Article
- Article
- In vivo disruption of latent HSV by designer endonuclease therapy.JCI insight · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Following acute infection, herpes simplex virus (HSV) establishes latency in sensory neurons, from which it can reactivate and cause recurrent disease. Available antiviral therapies do not affect latent viral genomes; therefore, they do not prevent reactivation following therapy cessation. One possible curative approach involves the introduction of DNA double strand breaks in latent HSV genomes by rare-cutting endonucleases, leading to mutagenesis of essential viral genes. We tested this approach in an in vitro HSV latency model using the engineered homing endonuclease (HE) HSV1m5, which recognizes a sequence in the HSV-1 gene UL19, encoding the virion protein VP5. Coexpression of the 3'-exonuclease Trex2 with HEs increased HE-mediated mutagenesis frequencies up to sixfold. Following HSV1m5/Trex2 delivery with adeno-associated viral (AAV) vectors, the target site was mutated in latent HSV genomes with no detectable cell toxicity. Importantly, HSV production by latently infected cells after reactivation was decreased after HSV1m5/Trex2 exposure. Exposure to histone deacetylase inhibitors prior to HSV1m5/Trex2 treatment increased mutagenesis frequencies of latent HSV genomes another two- to fivefold, suggesting that chromatin modification may be a useful adjunct to gene-targeting approaches. These results support the continuing development of HEs and other nucleases (ZFNs, TALENs, CRISPRs) for cure of chronic viral infections.Molecular Therapy-Nucleic Acids (2014) 3, e1; doi:10.1038/mtna.2013.75; published online 4 February 2014.
Identifiers
What OpenQuestion holds
Registered trials
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.