Academic Journal
Lipid Nanoparticles Deliver mRNA to the Brain after an Intracerebral Injection
| العنوان: | Lipid Nanoparticles Deliver mRNA to the Brain after an Intracerebral Injection |
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| المؤلفون: | Jan Tuma, Yu-Ju Chen, Michael G. Collins, Abhik Paul, Jie Li, Hesong Han, Rohit Sharma, Niren Murthy, Hye Young Lee |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | Biophysics, Cell Biology, Genetics, Molecular Biology, Neuroscience, Pharmacology, Biotechnology, Mental Health, Space Science, Biological Sciences not elsewhere classified, safer toxicity profile, often debilitating conditions, direct intracerebral injections, striatum (∼ 7, striatum (∼ 52, shows great promise, hippocampus (∼ 49, hippocampus (∼ 3, promising delivery vector, mc3 lnp mrnas, treating neurological disorders, based mrna delivery, neurological disorders, entire striatum, great potential, employ mc3, based therapeutics, mediated delivery, penetrated along, palliative rather |
| الوصف: | Neurological disorders are often debilitating conditions with no cure. The majority of current therapies are palliative rather than disease-modifying; therefore, new strategies for treating neurological disorders are greatly needed. mRNA-based therapeutics have great potential for treating such neurological disorders; however, challenges with delivery have limited their clinical potential. Lipid nanoparticles (LNPs) are a promising delivery vector for the brain, given their safer toxicity profile and higher efficacy. Despite this, very little is known about LNP-mediated delivery of mRNA into the brain. Here, we employ MC3-based LNPs and successfully deliver Cre mRNA and Cas9 mRNA/Ai9 sgRNA to the adult Ai9 mouse brain; greater than half of the entire striatum and hippocampus was found to be penetrated along the rostro-caudal axis by direct intracerebral injections of MC3 LNP mRNAs. MC3 LNP Cre mRNA successfully transfected cells in the striatum (∼52% efficiency) and hippocampus (∼49% efficiency). In addition, we demonstrate that MC3 LNP Cas9 mRNA/Ai9 sgRNA edited cells in the striatum (∼7% efficiency) and hippocampus (∼3% efficiency). Further analysis demonstrates that MC3 LNPs mediate mRNA delivery to multiple cell types including neurons, astrocytes, and microglia in the brain. Overall, LNP-based mRNA delivery is effective in brain tissue and shows great promise for treating complex neurological disorders. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| Relation: | https://figshare.com/articles/journal_contribution/Lipid_Nanoparticles_Deliver_mRNA_to_the_Brain_after_an_Intracerebral_Injection/24864666 |
| DOI: | 10.1021/acs.biochem.3c00371.s001 |
| الاتاحة: | https://doi.org/10.1021/acs.biochem.3c00371.s001 https://figshare.com/articles/journal_contribution/Lipid_Nanoparticles_Deliver_mRNA_to_the_Brain_after_an_Intracerebral_Injection/24864666 |
| Rights: | CC BY-NC 4.0 |
| رقم الانضمام: | edsbas.2B4F1B6F |
| قاعدة البيانات: | BASE |
| DOI: | 10.1021/acs.biochem.3c00371.s001 |
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