Academic Journal

A Non-Viral Plasmid DNA Delivery System Consisting on a Lysine-Derived Cationic Lipid Mixed with a Fusogenic Lipid

التفاصيل البيبلوغرافية
العنوان: A Non-Viral Plasmid DNA Delivery System Consisting on a Lysine-Derived Cationic Lipid Mixed with a Fusogenic Lipid
المؤلفون: Martínez-Negro, M. (María), Sánchez-Arribas, N. (Natalia), Guerrero-Martínez, A. (Andrés), Moyá, M.L. (María Luisa), Tros-de-Ilarduya, C. (Conchita), Mendicuti, F. (Francisco), Aicart, E. (Emilio), Junquera, E. (Elena)
بيانات النشر: MDPI AG
سنة النشر: 2019
المجموعة: dadun - Depósito Académico Digital Universidad de Navarra
مصطلحات موضوعية: Materias Investigacion::Farmacia::Química farmacéutica, Compaction, Gene delivery, Lipoplex, Lysine-derived cationic lipid, Molecular dynamics, Multilamellar aggregates, Plasmid DNA, Protection, Transfection
الوصف: The insertion of biocompatible amino acid moieties in non-viral gene nanocarriers is an attractive approach that has been recently gaining interest. In this work, a cationic lipid, consisting of a lysine-derived moiety linked to a C12 chain (LYCl) was combined with a common fusogenic helper lipid (DOPE) and evaluated as a potential vehicle to transfect two plasmid DNAs (encoding green fluorescent protein GFP and luciferase) into COS-7 cells. A multidisciplinary approach has been followed: (i) biophysical characterization based on zeta potential, gel electrophoresis, small-angle X-ray scattering (SAXS), and cryo-transmission electronic microscopy (cryo-TEM); (ii) biological studies by fluorescence assisted cell sorting (FACS), luminometry, and cytotoxicity experiments; and (iii) a computational study of the formation of lipid bilayers and their subsequent stabilization with DNA. The results indicate that LYCl/DOPE nanocarriers are capable of compacting the pDNAs and protecting them efficiently against DNase I degradation, by forming Lα lyotropic liquid crystal phases, with an average size of ~200 nm and low polydispersity that facilitate the cellular uptake process. The computational results confirmed that the LYCl/DOPE lipid bilayers are stable and also capable of stabilizing DNA fragments via lipoplex formation, with dimensions consistent with experimental values. The optimum formulations (found at 20% of LYCl content) were able to complete the transfection process efficiently and with high cell viabilities, even improving the outcomes of the positive control Lipo2000*.
نوع الوثيقة: article in journal/newspaper
وصف الملف: application/pdf
اللغة: English
Relation: https://hdl.handle.net/10171/61973
الاتاحة: https://hdl.handle.net/10171/61973
Rights: info:eu-repo/semantics/openAccess
رقم الانضمام: edsbas.3467B378
قاعدة البيانات: BASE