Evidence map›Paper›PMID 40510594›Full record

ArticleMolecular therapy. Nucleic acids2025

CRISPR antiviral inhibits neurotrophic JC polyomavirus in 2D and 3D culture models through dual-gRNA excision by SaCas9.

Angela Rocchi, Shuren Liao, Hong Liu, Chen Chen, Senem Çakır, Anna Bellizzi, Hassen S Wollebo, Ilker K Sariyer, Kamel Khalili

Abstract read
In one paragraph

Article in Molecular therapy. Nucleic acids, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

9 authors.

Angela RocchiDepartment of Microbiology, Immunology and Inflammation, Center for Neurovirology and Gene Editing, Temple University Lewis Katz School of Medicine, Philadelphia, PA 19140, USA.
Shuren LiaoDepartment of Microbiology, Immunology and Inflammation, Center for Neurovirology and Gene Editing, Temple University Lewis Katz School of Medicine, Philadelphia, PA 19140, USA.
Hong LiuDepartment of Microbiology, Immunology and Inflammation, Center for Neurovirology and Gene Editing, Temple University Lewis Katz School of Medicine, Philadelphia, PA 19140, USA.
Chen ChenDepartment of Microbiology, Immunology and Inflammation, Center for Neurovirology and Gene Editing, Temple University Lewis Katz School of Medicine, Philadelphia, PA 19140, USA.
Senem ÇakırDepartment of Microbiology, Immunology and Inflammation, Center for Neurovirology and Gene Editing, Temple University Lewis Katz School of Medicine, Philadelphia, PA 19140, USA.
Anna BellizziDepartment of Microbiology, Immunology and Inflammation, Center for Neurovirology and Gene Editing, Temple University Lewis Katz School of Medicine, Philadelphia, PA 19140, USA.
Hassen S WolleboDepartment of Microbiology, Immunology and Inflammation, Center for Neurovirology and Gene Editing, Temple University Lewis Katz School of Medicine, Philadelphia, PA 19140, USA.
Ilker K SariyerDepartment of Microbiology, Immunology and Inflammation, Center for Neurovirology and Gene Editing, Temple University Lewis Katz School of Medicine, Philadelphia, PA 19140, USA.
Kamel KhaliliDepartment of Microbiology, Immunology and Inflammation, Center for Neurovirology and Gene Editing, Temple University Lewis Katz School of Medicine, Philadelphia, PA 19140, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Without an effective antiviral, JC virus (JCV) has persisted throughout multiple epochs of immunosuppression, causing the opportunistic demyelinating disease, progressive multifocal leukoencephalopathy (PML). This study proposes a novel therapy using a dual-gRNA, SaCas9, CRISPR antiviral targeting JCV transcription factor, large tumor antigen (LT-Ag), and capsid protein, viral protein 1 (VP1). This treatment was validated using traditional two-dimensional cell culture. A recombinant cell line was produced from SVG astrocytes (SVGA) via lentiviral inoculation and puromycin selection. Following infection, sanger sequencing identified uniform excision of the circular dsDNA genome of JCV, significantly reducing viral load per genomic copy number on qPCR, viral proteins on western blot, and infectivity of viral progeny on adoptive transfer. Following this proof-of-concept using cell lines, translatability of results was advanced using three-dimensional, heterogeneous cerebral organoids (COs). COs were infected and treated with the lentivirus-packaged CRISPR antiviral. As observed in monolayer culture, a truncated genome was confirmed with sequencing, reducing viral load per genomic copy number on qPCR, protein levels on immunofluorescent imaging, and infectivity on adoptive transfer. The high efficacy of this JCV-targeting CRISPR antiviral in the context of cerebral organoids expounds on its value for the currently untreatable JCV and PML.

Indexed as

antiviralcerebral organoidsCRISPRgene editingJC virusMT: RNA/DNA Editingprogressive multifocal leukoencephalopathy

Identifiers

PMID40510594
PMCPMC12159223

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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.