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Article

Preparation and In Vitro Evaluation of RITUXfab-Decorated Lipoplexes to Improve Delivery of siRNA Targeting C1858T PTPN22 Variant in B Lymphocytes

1
Infectivology and Clinical Trials Research Department, Bambino Gesù Children’s Hospital, Scientific Institute for Research, Hospitalization and Healthcare (IRCCS), 00146 Rome, Italy
2
Research Centre on Bioactive Peptides (CIRPeB), Department of Pharmacy, University of Naples Federico II, 80134 Naples, Italy
3
Institute of Biostructures and Bioimaging (IBB), National Research Council (CNR), 80134 Naples, Italy
4
Confocal Microscopy Core Facility, Research Laboratories, Bambino Gesù Children’s Hospital, Scientific Institute for Research, Hospitalization and Healthcare (IRCCS), 00146 Rome, Italy
5
Research Laboratories, Bambino Gesù Children’s Hospital, Scientific Institute for Research, Hospitalization and Healthcare (IRCCS), 00146 Rome, Italy
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Unit of Hospital Pharmacy, Bambino Gesù Children’s Hospital, Scientific Institute for Research, Hospitalization and Healthcare (IRCCS), 00165 Rome, Italy
7
Diabetes and Growth Pathology Unit, Bambino Gesù Children’s Hospital, Scientific Institute for Research, Hospitalization and Healthcare (IRCCS), 00165 Rome, Italy
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Arcangelo Liso
Int. J. Mol. Sci. 2022, 23(1), 408; https://doi.org/10.3390/ijms23010408
Received: 1 December 2021 / Revised: 23 December 2021 / Accepted: 27 December 2021 / Published: 30 December 2021
(This article belongs to the Special Issue Advances in Immunotherapeutic Approaches to Type 1 Diabetes 2.0)
Autoimmune endocrine disorders, such as type 1 diabetes (T1D) and thyroiditis, at present are treated with only hormone replacement therapy. This emphasizes the need to identify personalized effective immunotherapeutic strategies targeting T and B lymphocytes. Among the genetic variants associated with several autoimmune disorders, the C1858T polymorphism of the protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene, encoding for Lyp variant R620W, affects the innate and adaptive immunity. We previously exploited a novel personalized immunotherapeutic approach based on siRNA delivered by liposomes (lipoplexes) that selectively inhibit variant allele expression. In this manuscript, we improved lipoplexes carrying siRNA for variant C1858T by functionalizing them with Fab of Rituximab antibody (RituxFab-Lipoplex) to specifically target B lymphocytes in autoimmune conditions, such as T1D. RituxFab-Lipoplexes specifically bind to B lymphocytes of the human Raji cell line and of human PBMC of healthy donors. RituxFab-Lipoplexes have impact on the function of B lymphocytes of T1D patients upon CpG stimulation showing a higher inhibitory effect on total cell proliferation and IgM+ plasma cell differentiation than the not functionalized ones. These results might open new pathways of applicability of RituxFab-Lipoplexes, such as personalized immunotherapy, to other autoimmune disorders, where B lymphocytes are the prevalent pathogenic immunocytes. View Full-Text
Keywords: T1D; autoimmune disease; functionalized lipoplexes; rituximab; immunotherapy; variant PTPN22 T1D; autoimmune disease; functionalized lipoplexes; rituximab; immunotherapy; variant PTPN22
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MDPI and ACS Style

Arena, A.; Belcastro, E.; Accardo, A.; Sandomenico, A.; Pagliarosi, O.; Rosa, E.; Petrini, S.; Conti, L.A.; Giorda, E.; Corsetti, T.; Schiaffini, R.; Morelli, G.; Fierabracci, A. Preparation and In Vitro Evaluation of RITUXfab-Decorated Lipoplexes to Improve Delivery of siRNA Targeting C1858T PTPN22 Variant in B Lymphocytes. Int. J. Mol. Sci. 2022, 23, 408. https://doi.org/10.3390/ijms23010408

AMA Style

Arena A, Belcastro E, Accardo A, Sandomenico A, Pagliarosi O, Rosa E, Petrini S, Conti LA, Giorda E, Corsetti T, Schiaffini R, Morelli G, Fierabracci A. Preparation and In Vitro Evaluation of RITUXfab-Decorated Lipoplexes to Improve Delivery of siRNA Targeting C1858T PTPN22 Variant in B Lymphocytes. International Journal of Molecular Sciences. 2022; 23(1):408. https://doi.org/10.3390/ijms23010408

Chicago/Turabian Style

Arena, Andrea, Eugenia Belcastro, Antonella Accardo, Annamaria Sandomenico, Olivia Pagliarosi, Elisabetta Rosa, Stefania Petrini, Libenzio Adrian Conti, Ezio Giorda, Tiziana Corsetti, Riccardo Schiaffini, Giancarlo Morelli, and Alessandra Fierabracci. 2022. "Preparation and In Vitro Evaluation of RITUXfab-Decorated Lipoplexes to Improve Delivery of siRNA Targeting C1858T PTPN22 Variant in B Lymphocytes" International Journal of Molecular Sciences 23, no. 1: 408. https://doi.org/10.3390/ijms23010408

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