Evidence map›Paper›PMID 35694213›Full record

ArticleMolecular therapy. Nucleic acids2022

Antisense transcription from lentiviral gene targeting linked to an integrated stress response in colorectal cancer cells.

Taekyu Ha, Michael DiPrima, Vishal Koparde, Parthav Jailwala, Hidetaka Ohnuki, Jing-Xin Feng, Murali Palangat, Daniel Larson, Giovanna Tosato

Open access · goldAbstract read
In one paragraph

Article in Molecular therapy. Nucleic acids, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.2field-weighted citation impact, top 53% 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

5 citing papers in PubMed, 3 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Non-coding antisense transcripts: fine regulation of gene expression in cancer.Computational and structural biotechnology journal · 2022
    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 at 2 institutions in 1 country.

Taekyu HaLaboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 37 Convent Drive, Bethesda, MD 20892, USA.
Michael DiPrimaLaboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 37 Convent Drive, Bethesda, MD 20892, USA.
Vishal KopardeCCR Collaborative Bioinformatics Resource, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Parthav JailwalaCCR Collaborative Bioinformatics Resource, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Hidetaka OhnukiLaboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 37 Convent Drive, Bethesda, MD 20892, USA.
Jing-Xin FengLaboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 37 Convent Drive, Bethesda, MD 20892, USA.
Murali PalangatLaboratory of Receptor Biology and Gene Expression, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Daniel LarsonLaboratory of Receptor Biology and Gene Expression, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Giovanna TosatoLaboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 37 Convent Drive, Bethesda, MD 20892, USA.
National Institutes of Health · USLeidos (United States) · US

Funding

Angiogenesis and Tumor GrowthZIASC010355 · NCI · DIVISION OF CLINICAL SCIENCES - NCI · PI TOSATO, GIOVANNA · 2009 to 2025
$13.3M
Study of the Roles of SDF1 and CXCR4 in HematopoiesisZIABC010782 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI TOSATO, GIOVANNA · 2009 to 2025
$10.2M
6 · The paper itself

Abstract

Advances in gene therapy research have resulted in the successful development of new therapies for clinical use. Here, we explored a gene targeting approach to deplete ephrinB2 from colorectal cancer cells using an inducible lentiviral vector. EphrinB2, a transmembrane ephrin ligand, promotes colorectal cancer cell growth and viability and predicts poor patient survival when expressed at high levels in colorectal cancer tissues. We discovered that lentiviral vector integration and expression in the host DNA frequently drive divergent host gene transcription, generating antisense reads coupled with splicing events and generation of chimeric vector/host transcripts. Antisense transcription of host DNA was linked to development of an integrated stress response and cell death. Despite recent successes, off-target effects remain a concern in genetic medicine. Our results provide evidence that divergent gene transcription is a previously unrecognized off-target effect of lentiviral vector integration with built-in properties for regulation of gene expression.

Indexed as

antisense readscolorectal cancerephrinB2gene therapyintegrated stress responselentiviral vectorMT: OligonucleotidesshRNATherapies and Applicationsvector integration

Identifiers

PMID35694213
PMCPMC9163427
OpenAlexW4280618080

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.