دورية أكاديمية
Improvement of Lipoplexes With a Sialic Acid Mimetic to Target the C1858T PTPN22 Variant for Immunotherapy in Endocrine Autoimmunity
| العنوان: | Improvement of Lipoplexes With a Sialic Acid Mimetic to Target the C1858T PTPN22 Variant for Immunotherapy in Endocrine Autoimmunity |
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| المؤلفون: | Arena, Andrea, Belcastro, Eugenia, Ceccacci, Francesca, Petrini, Stefania, Conti, Libenzio Adrian, Pagliarosi, Olivia, Giorda, Ezio, Sennato, Simona, Schiaffini, Riccardo, Wang, Peng, Paulson, James C, Mancini, Giovanna, Fierabracci, Alessandra |
| المساهمون: | Arena, Andrea, Belcastro, Eugenia, Ceccacci, Francesca, Petrini, Stefania, Conti, Libenzio Adrian, Pagliarosi, Olivia, Giorda, Ezio, Sennato, Simona, Schiaffini, Riccardo, Wang, Peng, Paulson, James C, Mancini, Giovanna, Fierabracci, Alessandra |
| سنة النشر: | 2022 |
| المجموعة: | ARPI - Archivio della Ricerca dell'Università di Pisa |
| مصطلحات موضوعية: | PEGylated lipid F9, T1D, functionalized lipoplexe, immunotherapy, variant PTPN22 |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/35355982; info:eu-repo/semantics/altIdentifier/wos/WOS:000776577900001; volume:13; firstpage:838331; journal:FRONTIERS IN IMMUNOLOGY; https://hdl.handle.net/11568/1181867Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85127239292 |
| DOI: | 10.3389/fimmu.2022.838331 |
| الإتاحة: | https://doi.org/10.3389/fimmu.2022.838331Test https://hdl.handle.net/11568/1181867Test |
| رقم الانضمام: | edsbas.BAEBAA14 |
| قاعدة البيانات: | BASE |
| DOI: | 10.3389/fimmu.2022.838331 |
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