{"doi":"10.1021/acs.biochem.3c00371","title":"Lipid Nanoparticles Deliver mRNA to the Brain after an Intracerebral Injection","abstract":"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.","journal":"Biochemistry","year":2023,"id":319038,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":59,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9516,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1027167,"name":"Y Chen","orcid":"0000-0002-1197-1086","position":1,"is_corresponding":false},{"id":1027168,"name":"Michael G. Collins","orcid":"0000-0002-3161-0595","position":2,"is_corresponding":false},{"id":1027169,"name":"Abhik Paul","orcid":"0000-0003-3797-2439","position":3,"is_corresponding":false},{"id":320283,"name":"Jie Li","orcid":"0000-0003-0189-2787","position":4,"is_corresponding":false},{"id":492016,"name":"Hesong Han","orcid":"0000-0001-5545-5238","position":5,"is_corresponding":false},{"id":708840,"name":"Rohit Sharma","orcid":"0000-0003-1428-5521","position":6,"is_corresponding":false},{"id":235839,"name":"Niren Murthy","orcid":"0000-0002-7815-7337","position":7,"is_corresponding":false},{"id":537536,"name":"Hye Young Lee","orcid":"0000-0002-3150-6886","position":8,"is_corresponding":false},{"id":537535,"name":"Jan Tůma","orcid":"0000-0002-7197-8482","position":0,"is_corresponding":true}],"reference_count":44,"raw_metadata":null,"created_at":"2026-07-19T01:07:06.454099Z","pmid":"37729550","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}