mRNA loaded Lipid Nanocapsules: a promising strategy to treat genetic diseases such as Pseudoxanthoma elasticum

التفاصيل البيبلوغرافية
العنوان: mRNA loaded Lipid Nanocapsules: a promising strategy to treat genetic diseases such as Pseudoxanthoma elasticum
المؤلفون: Zarikian, Laura, Delalande, Anthony, Pichon, Chantal, Martin, Ludovic, Lepeltier, Elise
المساهمون: Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Université d'Angers, Faculté de Santé, Département Pharmacie, Université d'Angers (UA), Université d'Orléans (UO), Institut universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.)
المصدر: SF Nano 2024 ; https://hal.science/hal-04841010 ; SF Nano 2024, Dec 2024, Toulouse, France
بيانات النشر: CCSD
سنة النشر: 2024
المجموعة: Université d'Orléans: HAL
مصطلحات موضوعية: Lipid nanoparticle, Lipid nanocapsules LNC, Rare disease, MRNA delivery, [SPI.NANO]Engineering Sciences [physics]/Micro and nanotechnologies/Microelectronics, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences
جغرافية الموضوع: Toulouse, France
الوصف: International audience ; Pseudoxanthoma elasticum (PXE) is a rare genetic disorder characterized by progressive ectopic calcification, which is caused by mutations in the ABCC6 gene. PXE predominantly affects the elastic fibers of the skin, Bruch’s membrane in the retina and the cardiovascular system [1]. Unfortunately, no curative treatment exists. To compensate the deficiency of the protein normally expressed in hepatocytes, the delivery of the corresponding mRNA has emerged as a promising therapeutic strategy. However, this approach requires a nanocarrier to cross the cell membrane, protect the mRNA, and ensure delivery to the targeted tissues.During the Covid-19 pandemic, lipid nanoparticles (LNP) highlighted the huge potential of nanomedicines: they successfully demonstrated their ability to protect and deliver mRNA. Among LNP, lipid nanocapsules (LNC) were designed and patented in 2014 by the MINT laboratory (patent FR 3026009 (A1)) [2] with the goal of protecting genetic material such as DNA, siRNA, and miRNA.The objective of this project is to formulate and characterize mRNA loaded LNC, assessing their in vitro toxicity on the hepatocyte cell lines HepG2 and SNU-387 and to validate the therapeutic strategy in Abcc6−/− mice.As a model to validate the formulation, mRNA encoding Enhanced Green Fluorescent Protein (EGFP) was initially used. In parallel, a total of 948.2 µg of ABCC6 mRNA was produced in Prof. Pichon’s laboratory. Both ABCC6 and EGFP mRNA-loaded LNC were fully characterized. Afterwards, a dose-dependent cytotoxicity was evaluated via MTT and LDH assays, with an IC50 of 1 mg/mL. Cell internalization studies using flow cytometry revealed an efficient uptake of DiD-labeled EGFP mRNA loaded LNC over time with a 100% internalization after 8 hours. Finally, in vivo studies were conducted in healthy mice by intravenous injection of DiD-labeled LNC. The results showed a significant accumulation of LNC in the liver 24 hours post-injection: ABCC6 being predominantly expressed in the liver, this ...
نوع الوثيقة: conference object
اللغة: English
الاتاحة: https://hal.science/hal-04841010
رقم الانضمام: edsbas.3E859E58
قاعدة البيانات: BASE