Exploiting novel tailored immunotherapies of type 1 diabetes: Short interfering RNA delivered by cationic liposomes enables efficient down-regulation of variant PTPN22 gene in T lymphocytes
| Autor: | Giovanna Mancini, Serena De Santis, Stefania Petrini, Alessandra Fierabracci, Marsha Pellegrino, Marco Cappa, Anita Scipioni, Francesca Ceccacci |
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| Přispěvatelé: | Pellegrino, M., Ceccacci, F., Petrini, S., Scipioni, A., De Santis, S., Cappa, M., Mancini, G., Fierabracci, A. |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Male
Small interfering RNA T-Lymphocytes medicine.medical_treatment Pharmaceutical Science Medicine (miscellaneous) 02 engineering and technology medicine.disease_cause Autoimmunity Immunotherapy Lipoplexes T1D Variant PTPN22 General Materials Science Cationic liposome RNA Small Interfering Child 0303 health sciences biology Chemistry Transfection Lipid 021001 nanoscience & nanotechnology Lipids Liposome Child Preschool Molecular Medicine Female 0210 nano-technology Human Adolescent CD3 Biomedical Engineering Down-Regulation Bioengineering PTPN22 03 medical and health sciences Cations medicine Humans RNA Messenger 030304 developmental biology immunotherapy lipoplexes variant PTPN22 Cation Base Sequence T-cell receptor Protein Tyrosine Phosphatase Non-Receptor Type 22 Dynamic Light Scattering Lipoplexe Diabetes Mellitus Type 1 T-Lymphocyte Liposomes Cancer research biology.protein |
| Zdroj: | Nanomedicine (Online) 18 (2019): 371–379. doi:10.1016/j.nano.2018.11.001 info:cnr-pdr/source/autori:Pellegrino M. (a); Ceccacci F. (b); Petrini S. (c); Scipioni A. (d); De Santis S. (d); Cappa M. (e); Mancini G. (f); Fierabracci A. (a)/titolo:Exploiting novel tailored immunotherapies of type 1 diabetes: Short interfering RNA delivered by cationic liposomes enables efficient down-regulation of variant PTPN22 gene in T lymphocytes/doi:10.1016%2Fj.nano.2018.11.001/rivista:Nanomedicine (Online)/anno:2019/pagina_da:371/pagina_a:379/intervallo_pagine:371–379/volume:18 |
| Popis: | In autoimmune diseases as Type 1 diabetes, the actual treatment that provides the missing hormones is not able, however, to interrupt the underlining immunological mechanism. Importantly, novel immunotherapies are exploited to protect and rescue the remaining hormone producing cells. Among probable targets of immunotherapy, the C1858T mutation in the PTPN22 gene, which encodes for the lymphoid tyrosine phosphatase (Lyp) variant R620W, reveals an autoimmunity related pathophysiological role. Our scope was to establish new C1858T PTPN22 siRNA duplexes delivered by liposomal carriers (lipoplexes) to patients' PBMC. Following lipoplexes treatment, CD3+ and CD3- immunotypes were efficiently transfected; cell integrity and viability were preserved. Specific target mRNA down-modulation was observed. After T cell receptor stimulation, in lipoplexes-treated PBMC Lyp function was restored by increased release of IL-2 in cultures. Results set-up the stage for ultimate trials in the treatment of autoimmunity based on the specific inhibitory targeting of C1858T PTPN22 by lipoplexes. |
| Databáze: | OpenAIRE |
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