Evidence map›Paper›PMID 36321136›Full record

ArticleMolecular therapy oncolytics2022

Enhanced genomic stability of new miRNA-regulated oncolytic coxsackievirus B3.

Huitao Liu, Amirhossein Bahreyni, Yasir Mohamud, Yuan Chao Xue, William W G Jia, Honglin Luo

Abstract read
In one paragraph

Article in Molecular therapy oncolytics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

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3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

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4 · The record

Corrections and comments

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5 · Who and what money

Authors and funding

6 authors.

Huitao LiuCentre for Heart Lung Innovation, St Paul's Hospital, Vancouver, BC V6Z 1Y6, Canada.
Amirhossein BahreyniCentre for Heart Lung Innovation, St Paul's Hospital, Vancouver, BC V6Z 1Y6, Canada.
Yasir MohamudCentre for Heart Lung Innovation, St Paul's Hospital, Vancouver, BC V6Z 1Y6, Canada.
Yuan Chao XueCentre for Heart Lung Innovation, St Paul's Hospital, Vancouver, BC V6Z 1Y6, Canada.
William W G JiaVirogin Biotech Ltd, Vancouver, BC V6S 2L9, Canada.
Honglin LuoCentre for Heart Lung Innovation, St Paul's Hospital, Vancouver, BC V6Z 1Y6, Canada.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Genetic modification of coxsackievirus B3 (CVB3) by inserting target sequences (TS) of tumor-suppressive and/or organ-selective microRNAs (miRs) into viral genome can efficiently eliminate viral pathogenesis without significant impacts on its oncolytic activity. Nonetheless, reversion mutants (loss of miR-TS inserts) were identified as early as day 35 post-injection in ∼40% immunodeficient mice. To improve the stability, here we re-engineered CVB3 by (1) replacing the same length of viral genome at the non-coding region with TS of cardiac-selective miR-1/miR-133 and pancreas-enriched miR-216/miR-375 or (2) inserting the above miR-TS into the coding region (i.e., P1 region) of viral genome. Serial passaging of these newly established miR-CVB3s in cultured cells for 20 rounds demonstrated significantly improved stability compared with the first-generation miR-CVB3 with 5'UTR insertion of miR-TS. The safety and stability of these new miR-CVB3s was verified in immunocompetent mice. Moreover, we showed that these new viruses retained the ability to suppress lung tumor growth in a xenograft mouse model. Finally, we observed that miR-CVB3 with insertion in P1 region was more stable than miR-CVB3 with preserved length of the 5'UTR, whereas the latter displayed significantly higher oncolytic activity. Overall, we presented here valid strategies to enhance the genomic stability of miR-CVB3 for virotherapy.

Indexed as

coxsackievirus B3cytotoxicitygenomic stabilitylung cancermiRNAoncolytic activityoncolytic virus

Identifiers

PMID36321136
PMCPMC9593271

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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.