Design of experiments to select triphenylphosphonium-polyplexes with suitable physicochemical properties for mitochondrial gene therapy

Publication date: 15 March 2020Source: Journal of Molecular Liquids, Volume 302Author(s): Ângela Sousa, Rúben Faria, Tânia Albuquerque, Himanshu Bhatt, Swati Biswas, João A. Queiroz, Diana CostaAbstractMitochondrial gene therapy can be seen as a promising tool and a revolutionary approach towards mitochondrial diseases arising from mitochondrial DNA mutations. The conception of a viable and suitable mitochondrial targeted vector is imperative to turn this therapy clinically feasible. To accomplish this goal, different molecular weight polyethylenimines (PEI) have been conjugated with the mitochondriotropic agent triphenylphosphonium (TPP) and the interaction of this polycation with the ND1 (mitochondrially encoded NADH dehydrogenase 1 protein) plasmid DNA has been explored for the formation of nanometer complexes. In order to quickly, easily and with reduced costs find out the most adequate gene delivery vector, a design of experiments (DoE) tool has been explored. For each different molecular weight PEI delivery system, the nitrogen to phosphate groups' ratio (N/P) and the pDNA volume were selected as DoE inputs and the pDNA complexation capacity (CC), surface charge and polyplexes size were considered DoE outputs. The study revealed that the combination of high N/P ratios with lower pDNA volume of the inputs favors the formulation of optimal carriers after the output maximization of pDNA CC and positive surface charge and output minimization of the particle sizes. Moreo...
Source: Journal of Molecular Liquids - Category: Molecular Biology Source Type: research