{"doi":"10.1101/2022.12.07.518870","title":"Engineered retrovirus-like nanocarriers for messenger RNA delivery into neurons","abstract":"Abstract Systemic delivery of mRNAs into disease neurons is first limited by the blood-brain-barrier (BBB). Leukocyte-derived extracellular vesicles (EVs) can cross the BBB at inflammatory sites, emerging as promising carriers to target the disease brain. However, efficient mRNA loading into EVs and their uptake by neurons remain challenges. Here we incorporated inside EVs the endogenous retrovirus-like Arc protein capsids, stabilized by Arc 5’UTR RNA elements, to effectively load and deliver mRNAs. Produced from self-derived leukocytes, engineered retrotransposon Arc EVs (eraEVs) are immunologically inert with minimal clearance. Equipped with endothelial adhesion molecules from donor leukocytes, circulating eraEVs enter the brain enriching at neuro-inflammatory sites. During self-assembly, Arc recruits enveloping proteins onto eraEVs further promoting neuronal uptake. Possessing high effectiveness like viral vectors and biocompatibility as natural vesicles, eraEV-nanocarriers can be produced from virtually all donor cell types, potentially leading to the development of future clinical therapies for a range of diseases. Abstract Figure","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":300680,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9434,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":848035,"name":"Sijin Luozhong","orcid":"0000-0001-8697-9480","position":1,"is_corresponding":false},{"id":991250,"name":"Simian Cai","orcid":"0000-0001-9686-0635","position":2,"is_corresponding":false},{"id":991627,"name":"Ketaki Londhe","orcid":null,"position":3,"is_corresponding":false},{"id":991251,"name":"Nadine Elkasri","orcid":"0000-0002-4619-2429","position":4,"is_corresponding":false},{"id":611958,"name":"Robert D. Hawkins","orcid":"0000-0001-9089-8544","position":5,"is_corresponding":false},{"id":307083,"name":"Zhefan Yuan","orcid":"0000-0002-4724-6214","position":6,"is_corresponding":false},{"id":991628,"name":"Kai Su-Greene","orcid":null,"position":7,"is_corresponding":false},{"id":991252,"name":"Mache Cruz","orcid":"0000-0002-8757-9929","position":8,"is_corresponding":false},{"id":991253,"name":"Yu‐Wei Chang","orcid":"0000-0003-3333-5424","position":9,"is_corresponding":false},{"id":307085,"name":"Patrick McMullen","orcid":"0000-0002-4916-5979","position":10,"is_corresponding":false},{"id":991254,"name":"Chunyan Wu","orcid":"0000-0001-7018-7331","position":11,"is_corresponding":false},{"id":550844,"name":"Changwoo Seo","orcid":"0000-0003-3903-7452","position":12,"is_corresponding":false},{"id":550843,"name":"Akash Guru","orcid":"0000-0003-1915-3165","position":13,"is_corresponding":false},{"id":848038,"name":"Wenting Gao","orcid":"0009-0008-0900-6106","position":14,"is_corresponding":false},{"id":848036,"name":"Tara Sarmiento","orcid":"0009-0001-4505-9677","position":15,"is_corresponding":false},{"id":292521,"name":"Chris B. Schaffer","orcid":"0000-0002-7800-9596","position":16,"is_corresponding":false},{"id":292520,"name":"Nozomi Nishimura","orcid":"0000-0003-4342-9416","position":17,"is_corresponding":false},{"id":307283,"name":"Richard A. Cerione","orcid":"0000-0003-4512-5897","position":18,"is_corresponding":false},{"id":264521,"name":"Melissa R. Warden","orcid":"0000-0003-2240-3997","position":19,"is_corresponding":false},{"id":377139,"name":"Robert Langer","orcid":"0000-0003-1703-6707","position":20,"is_corresponding":false},{"id":307088,"name":"Shaoyi Jiang","orcid":"0000-0002-4017-6540","position":21,"is_corresponding":false},{"id":264517,"name":"Wenchao Gu","orcid":"0000-0002-0967-1682","position":0,"is_corresponding":true}],"reference_count":39,"raw_metadata":null,"created_at":"2026-07-19T00:31:53.559757Z","pmid":null,"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":[]}