Evidence map›Paper›PMID 41817895›Full record

ArticleJournal of neuro-oncology2026

MGMT downregulation by CRISPR/Cas13 RNA-guided RNA targeting enhances glioma cell sensitivity to TMZ chemotherapy.

Terry J Prins, Thomas J Lai, Tie Li, Addison Fisher, Blaine S C Eldred, Ryan Mostafavi, Linda M Liau, Robert A Chong, Phioanh Leia Nghiemphu, Timothy F Cloughesy and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of neuro-oncology, 2026. 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

12 authors.

Terry J Prins *Department of Neurology, University of California, Los Angeles, 10833 Le Conte Ave, BOX 957066, CHS 36-128, Los Angeles, CA, 90095-7066, USA.
Thomas J Lai *Department of Neurosurgery, University of California, Los Angeles, Los Angeles, CA, USA.
Tie LiDepartment of Neurology, University of California, Los Angeles, 10833 Le Conte Ave, BOX 957066, CHS 36-128, Los Angeles, CA, 90095-7066, USA.
Addison FisherDepartment of Neurology, University of California, Los Angeles, 10833 Le Conte Ave, BOX 957066, CHS 36-128, Los Angeles, CA, 90095-7066, USA.
Blaine S C EldredDepartment of Neurology, University of California, Los Angeles, 10833 Le Conte Ave, BOX 957066, CHS 36-128, Los Angeles, CA, 90095-7066, USA.
Ryan MostafaviDepartment of Neurology, University of California, Los Angeles, 10833 Le Conte Ave, BOX 957066, CHS 36-128, Los Angeles, CA, 90095-7066, USA.
Linda M LiauDepartment of Neurosurgery, University of California, Los Angeles, Los Angeles, CA, USA.
Robert A ChongDepartment of Neurology, University of California, Los Angeles, 10833 Le Conte Ave, BOX 957066, CHS 36-128, Los Angeles, CA, 90095-7066, USA.
Phioanh Leia NghiemphuDepartment of Neurology, University of California, Los Angeles, 10833 Le Conte Ave, BOX 957066, CHS 36-128, Los Angeles, CA, 90095-7066, USA.
Timothy F CloughesyDepartment of Neurology, University of California, Los Angeles, 10833 Le Conte Ave, BOX 957066, CHS 36-128, Los Angeles, CA, 90095-7066, USA.
David A NathansonDepartment of Medical and Molecular Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA.
Albert LaiDepartment of Neurology, University of California, Los Angeles, 10833 Le Conte Ave, BOX 957066, CHS 36-128, Los Angeles, CA, 90095-7066, USA. albertlai@mednet.ucla.edu.

Funding

UCLA SPORE in Brain CancerP50CA211015 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Yvonne Yu-Hsuan Chen · 2017 to 2026
$25.2M
NCI NIH HHS P50 CA211015NCI NIH HHS P50 CA211015-01A1
6 · The paper itself

Abstract

backgroundCurrent standard of care for glioblastoma involves fractionated radiotherapy administered with Temozolomide (TMZ), a DNA-alkylating agent. Inhibition of the DNA repair enzyme, O⁶-methylguanine-DNA methyltransferase (MGMT), promotes sensitivity to TMZ, particularly in tumors that repress MGMT mRNA transcription through promoter methylation. Novel strategies to inhibit MGMT are a promising avenue to improve therapeutic outcomes to TMZ. We hypothesized that CRISPR-Cas13-mediated RNA regulatory silencing of MGMT mRNA enhances response of immortalized and primary patient-derived gliomaspheres to TMZ in vitro.

methodsWe utilized the Cas13x and Cas13d variants to target MGMT mRNA in the MGMT-expressing LN18 glioma cell line and in two patient-derived gliomasphere lines (GS104, GS081). Cas13-guide RNA ribonucleoproteins were delivered via lipofection, and stable knockdown was achieved using a lentiviral all-in-one system. MGMT mRNA and protein downregulation were assessed by RT-PCR and Western blot, respectively. Cell viability and chemosensitivity to TMZ were evaluated using MTT assays.

resultsBoth Cas13x and Cas13d systems, directed by specific guide CRISPR RNAs, achieved rapid and potent knockdown of MGMT mRNA and protein in all tested cell lines. This downregulation of MGMT expression led to an increase in the cytotoxic effects of TMZ, sensitizing previously resistant glioma cells and patient-derived gliomaspheres to standard chemotherapy. The lentiviral Cas13d system established stable chemosensitization in gliomasphere models.

conclusionCRISPR-Cas13-mediated targeting of MGMT mRNA is an effective strategy for overcoming TMZ resistance in in vitro glioblastoma models. This RNA regulatory editing approach offers a proof-of-principle for CRISPR mediated therapeutics in patients with MGMT unmethylated gliomas.

Indexed as

Antineoplastic Agents, AlkylatingBrain NeoplasmsCRISPR-Cas SystemsDacarbazineDNA Modification MethylasesDNA Repair EnzymesGliomaTumor Suppressor ProteinsCell Line, TumorCell SurvivalDown-RegulationDrug Resistance, NeoplasmGene Expression Regulation, NeoplasticHumansRNA, Guide, CRISPR-Cas SystemsRNA, MessengerAntineoplastic Agents, AlkylatingDacarbazineDNA Modification MethylasesDNA Repair EnzymesMGMT protein, humanRNA, Guide, CRISPR-Cas SystemsRNA, MessengerTemozolomideTumor Suppressor ProteinsCRISPRGliomaMGMT-methylationRNA-guided RNA targetingTemozolomide

Identifiers

PMID41817895
PMCPMC12982228

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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.