Evidence map›Paper›PMID 38740820›Full record

ArticleNature communications2024

Gene editing for latent herpes simplex virus infection reduces viral load and shedding in vivo.

Martine Aubert, Anoria K Haick, Daniel E Strongin, Lindsay M Klouser, Michelle A Loprieno, Laurence Stensland, Tracy K Santo, Meei-Li Huang, Ollivier Hyrien, Daniel Stone and 1 more

Abstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed, 1 pooled it
–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

17 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Developments in genital herpes: progress in prevention and treatment.Current opinion in infectious diseases · 2026
    Review
  6. Article
  7. Review
  8. Review
  9. Review
  10. Article
  11. Review
  12. Review
  13. Article
  14. Article
  15. The HUSH epigenetic repressor complex silences PML nuclear body-associated HSV-1 quiescent genomes.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  16. Article
  17. Review
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

11 authors.

Martine AubertVaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, 98109, USA.ORCID http://orcid.org/0000-0003-1125-6856
Anoria K HaickVaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, 98109, USA.
Daniel E StronginDepartment of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, 98133, USA.
Lindsay M KlouserVaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, 98109, USA.ORCID http://orcid.org/0000-0002-9644-361X
Michelle A LoprienoVaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, 98109, USA.ORCID http://orcid.org/0000-0002-2905-485X
Laurence StenslandDepartment of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, 98133, USA.
Tracy K SantoDepartment of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, 98133, USA.
Meei-Li HuangDepartment of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, 98133, USA.
Ollivier HyrienVaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, 98109, USA.
Daniel StoneVaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, 98109, USA.ORCID http://orcid.org/0000-0003-1619-7541
Keith R JeromeVaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, 98109, USA. kjerome@fredhutch.org.ORCID http://orcid.org/0000-0002-8212-3789

Funding

Translational Bioimaging Core Shared ResourceP30CA015704 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Eric Collisson · 1985 to 2026
$296.4M
Wellstone Muscular Dystrophy Specialized Research Center (Seattle)P50AR065139 · NIAMS · UNIVERSITY OF WASHINGTON · PI JEFFREY S CHAMBERLAIN · 2018 to 2026
$15.9M
Endonuclease-mediated disruption of latent HSV as curative therapyR01AI132599 · NIAID · FRED HUTCHINSON CANCER RESEARCH CENTER · PI JEROME, KEITH R · 2018 to 2022
$2.6M
NCI NIH HHS P30 CA015704NIAID NIH HHS R01 AI132599NIAMS NIH HHS P50 AR065139
6 · The paper itself

Abstract

Anti-HSV therapies are only suppressive because they do not eliminate latent HSV present in ganglionic neurons, the source of recurrent disease. We have developed a potentially curative approach against HSV infection, based on gene editing using HSV-specific meganucleases delivered by adeno-associated virus (AAV) vectors. Gene editing performed with two anti-HSV-1 meganucleases delivered by a combination of AAV9, AAV-Dj/8, and AAV-Rh10 can eliminate 90% or more of latent HSV DNA in mouse models of orofacial infection, and up to 97% of latent HSV DNA in mouse models of genital infection. Using a pharmacological approach to reactivate latent HSV-1, we demonstrate that ganglionic viral load reduction leads to a significant decrease of viral shedding in treated female mice. While therapy is well tolerated, in some instances, we observe hepatotoxicity at high doses and subtle histological evidence of neuronal injury without observable neurological signs or deficits. Simplification of the regimen through use of a single serotype (AAV9) delivering single meganuclease targeting a duplicated region of the HSV genome, dose reduction, and use of a neuron-specific promoter each results in improved tolerability while retaining efficacy. These results reinforce the curative potential of gene editing for HSV disease.

Indexed as

DependovirusGene EditingHerpes SimplexHerpesvirus 1, HumanViral LoadVirus SheddingAnimalsDisease Models, AnimalDNA, ViralFemaleGenetic TherapyGenetic VectorsHerpes GenitalisHumansMiceVero CellsDNA, Viral

Identifiers

PMID38740820
PMCPMC11091195

What OpenQuestion holds

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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.