{"doi":"10.1016/j.ymthe.2020.12.023","title":"Docosanoic acid conjugation to siRNA enables functional and safe delivery to skeletal and cardiac muscles","abstract":"Oligonucleotide therapeutics hold promise for the treatment of muscle- and heart-related diseases. However, oligonucleotide delivery across the continuous endothelium of muscle tissue is challenging. Here, we demonstrate that docosanoic acid (DCA) conjugation of small interfering RNAs (siRNAs) enables efficient (~5% of injected dose), sustainable (>1 month), and non-toxic (no cytokine induction at 100 mg/kg) gene silencing in both skeletal and cardiac muscles after systemic injection. When designed to target myostatin (muscle growth regulation gene), siRNAs induced ~55% silencing in various muscle tissues and 80% silencing in heart, translating into a ~50% increase in muscle volume within 1 week. Our study identifies compounds for RNAi-based modulation of gene expression in skeletal and cardiac muscles, paving the way for both functional genomics studies and therapeutic gene modulation in muscle and heart.","journal":"Molecular Therapy","year":2020,"id":57871,"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":76,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9524,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":302202,"name":"Jillian Caiazzi","orcid":"0000-0002-7077-2116","position":1,"is_corresponding":false},{"id":302204,"name":"Nicholas McHugh","orcid":"0000-0003-2004-0811","position":2,"is_corresponding":false},{"id":302554,"name":"Vignesh Hariharan","orcid":"0000-0001-9624-1244","position":3,"is_corresponding":false},{"id":302555,"name":"Manish Muhuri","orcid":"0000-0003-3265-903X","position":4,"is_corresponding":false},{"id":302206,"name":"Anastasia Khvorova","orcid":"0000-0001-6928-8071","position":5,"is_corresponding":false},{"id":302201,"name":"Annabelle Biscans","orcid":"0000-0001-9953-9265","position":0,"is_corresponding":true}],"reference_count":75,"raw_metadata":null,"created_at":"2026-07-18T21:06:48.611399Z","pmid":"33348054","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":[]}