Cited by 30RNA Interference and Gene DeliveryGlioma Diagnosis and TreatmentNanoparticle-Based Drug Delivery

Intracranial delivery of synthetic mRNA to suppress glioblastoma

Open access
Peng, Hao, Guo, Xingrong, He, Jinjuan, Duan, Chao, Yang, Minghuan, Zhang, Xianghua, Zhang, Li, Fu, Rui +8 more·2022·Molecular Therapy - Oncolytics

Abstract

Owing to messenger RNA's unique biological advantages, it has received increasing attention to be used as a therapeutic, known as mRNA-based gene therapy. It is critical to have an ideal strategy of mRNA gene therapy for glioma, which grows in a special environment. In the present study, we screened out a safe and efficient transfection reagent for intracranial delivery of synthetic mRNA in mouse brain. First, in order to analyze the effect of different transfection reagents on the intracranial delivery of mRNA, the synthetic luciferase mRNA was wrapped with two different transfection reagents and microinjected into the brain at the fixed point. The expression status of delivered mRNA was monitored by a small animal imaging system. The possible reagent-induced biological toxicity was evaluated by behavioral and blood biochemical measurements. Then, to test the therapeutic effect of our intracranial delivery mRNA model on glioma, synthetic modified tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) mRNA was used as an example of therapeutic application. This model demonstrated that synthetic mRNA could be successfully delivered into the brain using commercially available transfection reagents, and TransIT-mRNA showed better results than in vivo -jetPEI kit. This model can be applied in precise targeting and personalized gene therapy of glioma.

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  • An intracerebral injection avoids the tissue barrier that the blood-CSF barrier or blood-brain-barrier represents and consequently should lead to significantly higher brain transfection levels by specifically targeting local regions of the brain.

    “An intracerebral injection avoids the tissue barrier that blood-cerebrospinal fluid (CSF) barrier or blood-brain-barrier (BBB) represents, and consequently should lead to significantly higher brain transfection levels by specifically targeting local regions of the brain (4, 20, 22, 26, 27).”

    From Lipid Nanoparticles Deliver mRNA to the Brain after an Intracerebral Injection (2023) · cites this paper as [4]

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  • Intracerebral injections are clinically feasible and are performed in a variety of clinical scenarios and preclinical settings.

    “Intracerebral injections are clinically feasible, and are performed in a variety of clinical scenarios (17–23), as well as in various preclinical settings (4, 24–27).”

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Cited by

Sorted by citations

Authors
Peng, H., Guo, X., He, J., Duan, C., Yang, M., Zhang, X., Zhang, L., Fu, R., Wang, B., Wang, D., Chen, H., Xie, M., Feng, P., Dai, L., Tang, X., & Luo, J.
Affiliations
Hubei University of Medicine (CN)
Corresponding author
  • Tang, Xiangjun
  • Luo, Jie
Venue
Molecular Therapy - Oncolytics
Publisher
Elsevier BV
Published
2022-03
Volume
24
Pages
160-170
ISSN
2372-7705 (ISSN-L)
OpenAlex
W4200040305
Cited by
30
References
3
Citations by year
2026: 3 · 2025: 9 · 2024: 3 · 2023: 12 · 2022: 3
FWCI
1.41
Type
journal article
Language
en
Open access
Locations
  • Molecular Therapy — Oncolytics (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Natural Science Foundation of China
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
  • Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
Keywords
glioblastoma, transfection reagents, transfection toxicity, personalized gene therapy

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