Intracranial delivery of synthetic mRNA to suppress glioblastoma
Open accessAbstract
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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Experimental — accuracy not yet measuredIntracerebral 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).”
From Lipid Nanoparticles Deliver mRNA to the Brain after an Intracerebral Injection (2023) · cites this paper as [4]
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Cited by
Sorted by citations
Han, E. L., Padilla, M. S., Palanki, R., Kim, D., Mrksich, K., Li, J. J., Tang, S., Yoon, I.-C., & Mitchell, M. J. (2024) · Nano Letters · doi:10.1021/acs.nanolett.3c03509 · Cited by 72 · see citing works
Lipid Nanoparticles Deliver mRNA to the Brain after an Intracerebral Injection
Tuma, J., Chen, Y.-J., Collins, M. G., Paul, A., Li, J., Han, H., Sharma, R., Murthy, N., & Lee, H. Y. (2023) · Biochemistry · doi:10.1021/acs.biochem.3c00371 · Cited by 65 · see citing works
- 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
- ORCID
- Venue
- Molecular Therapy - Oncolytics
- Publisher
- Elsevier BV
- Published
- 2022-03
- Volume
- 24
- Pages
- 160-170
- ISSN
- 2372-7705 (ISSN-L)
- PMC
- PMC8724946
- 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
- gold
- doi.org
- Licence
- 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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