{"doi":"10.3389/fimmu.2022.838331","title":"Improvement of Lipoplexes With a Sialic Acid Mimetic to Target the C1858T PTPN22 Variant for Immunotherapy in Endocrine Autoimmunity","abstract":"The C1858T variant of the protein tyrosine phosphatase N22 ( PTPN22 ) gene is associated with pathophysiological phenotypes in several autoimmune conditions, namely, Type 1 diabetes and autoimmune thyroiditis. The R620W variant protein, encoded by C1858T, leads to a gain of function mutation with paradoxical reduced T cell activation. We previously exploited a novel personalized immunotherapeutic approach based on siRNA delivered by liposomes (lipoplexes, LiposiRNA) that selectively inhibit variant allele expression. In this manuscript, we functionalize lipoplexes carrying siRNA for variant C1858T with a high affinity ligand of Siglec-10 (Sig10L) coupled to lipids resulting in lipoplexes (LiposiRNA-Sig10L) that enhance delivery to Siglec-10 expressing immunocytes. LiposiRNA-Sig10L lipoplexes more efficiently downregulated variant C1858T PTPN22 mRNA in PBMC of heterozygous patients than LiposiRNA without Sig10L. Following TCR engagement, LiposiRNA-Sig10L more significantly restored IL-2 secretion, known to be paradoxically reduced than in wild type patients, than unfunctionalized LiposiRNA in PBMC of heterozygous T1D patients.","journal":"Frontiers in Immunology","year":2022,"id":264015,"datarank":0.38474240361923057,"base_score":2.5649493574615367,"endowment":2.5649493574615367,"self_citation_contribution":0.38474240361923057,"citation_network_contribution":0.0,"self_endowment_contribution":0.38474240361923057,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":12,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.957,"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":921536,"name":"Eugenia Belcastro","orcid":"0000-0002-8154-3730","position":1,"is_corresponding":false},{"id":921537,"name":"Francesca Ceccacci","orcid":"0000-0003-3191-8562","position":2,"is_corresponding":false},{"id":921538,"name":"Stefania Petrini","orcid":"0000-0002-3249-0003","position":3,"is_corresponding":false},{"id":921539,"name":"Libenzio Adrian Conti","orcid":"0000-0001-9466-5473","position":4,"is_corresponding":false},{"id":921540,"name":"Olivia Pagliarosi","orcid":"0000-0002-9413-3124","position":5,"is_corresponding":false},{"id":921541,"name":"Ezio Giorda","orcid":"0000-0002-5875-832X","position":6,"is_corresponding":false},{"id":921542,"name":"Simona Sennato","orcid":"0000-0003-4793-5359","position":7,"is_corresponding":false},{"id":921543,"name":"Riccardo Schiaffini","orcid":"0000-0002-9527-2353","position":8,"is_corresponding":false},{"id":270756,"name":"Peng Wang","orcid":"0009-0009-0391-7379","position":9,"is_corresponding":false},{"id":230746,"name":"James C. Paulson","orcid":"0000-0003-4589-5322","position":10,"is_corresponding":false},{"id":921544,"name":"Giovanna Mancini","orcid":"0000-0001-8231-7949","position":11,"is_corresponding":false},{"id":921545,"name":"Alessandra Fierabracci","orcid":"0000-0003-3078-9754","position":12,"is_corresponding":false},{"id":921535,"name":"Andrea Arena","orcid":"0000-0002-0966-3332","position":0,"is_corresponding":true}],"reference_count":48,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:26:37.567338Z","pmid":"35355982","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":[]}