Lipid Nanoparticles Deliver mRNA to the Brain after an Intracerebral Injection.
Lipid Nanoparticles Deliver mRNA to the Brain after an Intracerebral Injection.
复制标题
脂质纳米颗粒在脑内注射后将 mRNA 递送至大脑。
DOI：
10.1021/acs.biochem.3c00371
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发表时间：
2023
期刊：
影响因子：
2.9
通讯作者：
Lee,HyeYoung
中科院分区：
文献类型：
--
作者：
Tuma,Jan;Chen,Yu-Ju;Collins,MichaelG;Paul,Abhik;Li,Jie;Han,Hesong;Sharma,Rohit;Murthy,Niren;Lee,HyeYoung
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.
