{"doi":"10.1002/smll.202405806","title":"PEGylated Multimeric RNA Nanoparticles for siRNA Delivery in Traumatic Brain Injury","abstract":"Traumatic brain injury (TBI) impacts millions of people globally, however currently there are no approved therapeutics that address long-term brain health. In order to create a technology that is relevant for siRNA delivery in TBI after systemic administration, sub-100 nm nanoparticles with rolling circle transcription (RCT) are synthesized and isolated in order improve payload delivery into the injured brain. Unlike conventional RCT-based RNA particles, in this method, sub-100 nm RNA nanoparticles (RNPs) are isolated. To enhance RNP pharmacokinetics, RNPs are synthesized with modified bases in order to graft polyethylene glycol (PEG) to the RNPs. PEGylated RNPs (PEG-RNPs) do not significantly impact their knockdown activity in vitro and lead to longer blood half-life after systemic administration and greater accumulation into the injured brain in a mouse model of TBI. In order to demonstrate RNA interference (RNAi) activity of RNPs, knockdown of the inflammatory cytokine TNF-α in injured brain tissue after systemic administration of RNPs in a mouse model of TBI is demonstrated. In summary, small sub-100 nm multimeric RNA nanoparticles are synthesized and isolated that can be modified using accessible chemistry in order to create a technology suitable for systemic RNAi therapy for TBI.","journal":"Small","year":2024,"id":441426,"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":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9538,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1253934,"name":"Woojung Yoo","orcid":"0000-0001-5787-4727","position":1,"is_corresponding":false},{"id":1254482,"name":"Olivia Carton","orcid":null,"position":2,"is_corresponding":false},{"id":1253935,"name":"Jinmyoung Joo","orcid":"0000-0003-1574-9842","position":3,"is_corresponding":false},{"id":577557,"name":"Ester J. Kwon","orcid":"0000-0002-6335-9681","position":4,"is_corresponding":false},{"id":1253933,"name":"Sang Woo Han","orcid":"0000-0001-5406-5211","position":0,"is_corresponding":true}],"reference_count":68,"raw_metadata":null,"created_at":"2026-07-19T02:01:06.281460Z","pmid":"39498752","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":[]}