Evidence map›Paper›PMID 32811834›Full record

ArticleNature communications2020

Gene editing and elimination of latent herpes simplex virus in vivo.

Martine Aubert, Daniel E Strongin, Pavitra Roychoudhury, Michelle A Loprieno, Anoria K Haick, Lindsay M Klouser, Laurence Stensland, Meei-Li Huang, Negar Makhsous, Alexander Tait and 6 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed
6.4field-weighted citation impact, top 2% 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

51 citing papers in PubMed, 76 citations in OpenAlex.

  1. In vivo CRISPR gene editing in patients with herpetic stromal keratitis.Molecular therapy : the journal of the American Society of Gene Therapy · 2023
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  12. 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
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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

16 authors at 3 institutions in 2 countries.

Martine AubertVaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.ORCID http://orcid.org/0000-0003-1125-6856
Daniel E StronginDepartment of Laboratory Medicine, University of Washington, Seattle, WA, USA.
Pavitra RoychoudhuryDepartment of Laboratory Medicine, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-4567-8232
Michelle A LoprienoVaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Anoria K HaickVaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Lindsay M KlouserVaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Laurence StenslandDepartment of Laboratory Medicine, University of Washington, Seattle, WA, USA.
Meei-Li HuangDepartment of Laboratory Medicine, University of Washington, Seattle, WA, USA.
Negar MakhsousDepartment of Laboratory Medicine, University of Washington, Seattle, WA, USA.
Alexander TaitDepartment of Laboratory Medicine, University of Washington, Seattle, WA, USA.
Harshana S De Silva FeelixgeVaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Roman GalettoCellectis SA, Paris, France.
Philippe DuchateauCellectis SA, Paris, France.ORCID http://orcid.org/0000-0002-3491-9168
Alexander L GreningerDepartment of Laboratory Medicine, University of Washington, Seattle, WA, USA.
Daniel StoneVaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.ORCID http://orcid.org/0000-0003-1619-7541
Keith R JeromeVaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. kjerome@fredhutch.org.ORCID http://orcid.org/0000-0002-8212-3789
University of Washington · USFred Hutch Cancer Center · USCape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa · ZA

Funding

Translational Bioimaging Core Shared ResourceP30CA015704 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Eric Collisson · 1985 to 2026
$296.4M
Cell and Gene Therapy for HIV CureUM1AI126623 · NIAID · FRED HUTCHINSON CANCER RESEARCH CENTER · PI JEROME, KEITH R, KIEM, HANS-PETER · 2016 to 2020
$24.2M
Endonuclease-mediated disruption of latent HSV as curative therapyR01AI132599 · NIAID · FRED HUTCHINSON CANCER RESEARCH CENTER · PI JEROME, KEITH R · 2018 to 2022
$2.6M
In vivo inactivation of latent HSV by endonuclease-mediated mutagenesisR21AI117519 · NIAID · FRED HUTCHINSON CANCER RESEARCH CENTER · PI JEROME, KEITH R · 2016 to 2017
$484k
NCI NIH HHS P30 CA015704NIAID NIH HHS R01 AI132599NIAID NIH HHS R21 AI117519NIAID NIH HHS UM1 AI126623
6 · The paper itself

Abstract

We evaluate gene editing of HSV in a well-established mouse model, using adeno-associated virus (AAV)-delivered meganucleases, as a potentially curative approach to treat latent HSV infection. Here we show that AAV-delivered meganucleases, but not CRISPR/Cas9, mediate highly efficient gene editing of HSV, eliminating over 90% of latent virus from superior cervical ganglia. Single-cell RNA sequencing demonstrates that both HSV and individual AAV serotypes are non-randomly distributed among neuronal subsets in ganglia, implying that improved delivery to all neuronal subsets may lead to even more complete elimination of HSV. As predicted, delivery of meganucleases using a triple AAV serotype combination results in the greatest decrease in ganglionic HSV loads. The levels of HSV elimination observed in these studies, if translated to humans, would likely significantly reduce HSV reactivation, shedding, and lesions. Further optimization of meganuclease delivery and activity is likely possible, and may offer a pathway to a cure for HSV infection.

Indexed as

AnimalsCells, CulturedChlorocebus aethiopsCRISPR-Cas SystemsDeoxyribonucleasesDependovirusEye InfectionsFemaleGene EditingHEK293 CellsHerpes SimplexHerpesvirus 1, HumanHumansMiceNeuronsRNA-SeqDeoxyribonucleases

Identifiers

PMID32811834
PMCPMC7435201
OpenAlexW3072707970

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.