Evidence map›Paper›PMID 40943604›Full record

ArticleInternational journal of molecular sciences2025

Disruption of Human Papillomavirus 16 E6/E7 Genes Using All-in-One Adenovirus Vectors Expressing Eight Double-Nicking Guide RNAs.

Megumi Yamaji, Tomomi Nakahara, Tomoko Nakanishi, Satomi Aoyama-Kikawa, Kiyoshi Yamaguchi, Yoichi Furukawa, Mariko Nakamura, Tadashi Okada, Hirotaka Tabata, Ryoko Fuse and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in International journal of molecular sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

Megumi YamajiCenter of Biomedical Research Resources, Juntendo University School of Medicine, Tokyo 113-8421, Japan.
Tomomi NakaharaNational Cancer Center Research Institute, Tokyo 466-0045, Japan.
Tomoko NakanishiCenter of Biomedical Research Resources, Juntendo University School of Medicine, Tokyo 113-8421, Japan.
Satomi Aoyama-KikawaNational Cancer Center Research Institute, Tokyo 466-0045, Japan.ORCID 0000-0002-0822-9593
Kiyoshi YamaguchiDivision of Clinical Genome Research, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
Yoichi FurukawaDivision of Clinical Genome Research, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.ORCID 0000-0003-0462-8631
Mariko NakamuraCenter of Biomedical Research Resources, Juntendo University School of Medicine, Tokyo 113-8421, Japan.
Tadashi OkadaDepartment of Pharmaceutical Engineering, Faculty of Engineering, Toyama Prefectural University, Toyama 939-0398, Japan.
Hirotaka TabataDepartment of Pharmaceutical Engineering, Faculty of Engineering, Toyama Prefectural University, Toyama 939-0398, Japan.
Ryoko FuseLaboratory of Virology, Institute of Microbial Chemistry (BIKAKEN), Microbial Chemistry Foundation, Tokyo 141-0021, Japan.
Eigo ShimizuDivision of Health Medical Intelligence, Human Genome Center, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
Rika KasajimaDivision of Health Medical Intelligence, Human Genome Center, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.ORCID 0000-0001-6389-6594
Seiya ImotoDivision of Health Medical Intelligence, Human Genome Center, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
Iwao KukimotoPathogen Genomics Center, National Institute of Infectious Diseases, Tokyo 208-0011, Japan.ORCID 0000-0001-9080-1642
Izumu SaitoDepartment of Physiology, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan.
Tohru KiyonoProject for Prevention of HPV-Related Cancer, Division of Collaborative Research and Development, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Chiba 277-8577, Japan.ORCID 0000-0003-1769-403X

Funding

Japan Agency for Medical Research and Development 20jk0210009h0001Japan Agency for Medical Research and Development JP21fk0108106Japan Agency for Medical Research and Development JP22fk0310523Japan Agency for Medical Research and Development (JP22ym0126804Japan Society for the Promotion of Science JP19K0647Japan Society for the Promotion of Science JP23H02402Japan Society for the Promotion of Science JP25K02541
6 · The paper itself

Abstract

Human papillomavirus (HPV) is a prime target for genome-editing therapy as its E6 and E7 oncogenes are crucial for cancer development and maintenance. A key challenge in CRISPR/Cas9 therapy is the off-target effects. This study utilized a double-nicking technique to introduce DNA breaks in the E6 and E7 regions of HPV16. From 146 gRNA candidates, 16 double-nicking pairs were selected. Multiple combinations of double-nicking (DN)-gRNA pairs were delivered to HPV16-positive cells via lentiviruses, followed by Cas9 nickase (Cas9n) expression. Combinations of 3-4 DN-gRNA pairs effectively killed HPV16-positive cells while sparing HPV-negative cells. Off-target effects were reduced by nearly three orders of magnitude. An "all-in-one" adenovirus (AdV) system expressing four gRNA pairs and Cas9n showed promise in inhibiting tumor growth in HPV16-positive cancer models, demonstrating its potential as a safe and effective treatment for HPV-induced tumors.

Indexed as

AdenoviridaeGenetic VectorsHuman papillomavirus 16Oncogene Proteins, ViralPapillomavirus E7 ProteinsRepressor ProteinsRNA, Guide, CRISPR-Cas SystemsAnimalsCell Line, TumorCRISPR-Cas SystemsFemaleGene EditingGenetic TherapyHumansMicePapillomavirus InfectionsE6 protein, Human papillomavirus type 16oncogene protein E7, Human papillomavirus type 16Oncogene Proteins, ViralPapillomavirus E7 ProteinsRepressor ProteinsRNA, Guide, CRISPR-Cas Systemsadenovirus vectorall-in-onecancer therapyCRISPR/Cas9gene therapygenome editinghuman papillomavirusmultiplex guide RNAnickase

Identifiers

PMID40943604
PMCPMC12429375

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Registered trials

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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.