Choice of an Effective Non-Viral System for the Delivery of siRNA to Multipotent Mesenchymal Stromal Cells

Abstract

Multipotent mesenchymal stromal cells (MSCs) can be used as a model for the development of gene and cell technologies and as a means of delivering nucleic acids to the body, including as part of tissue-engineering constructs. Small interfering RNA (siRNA) molecules acting by the RNA interference mechanism are a high-precision tool for genetic silencing of target mRNA transcripts. The search for low toxic and highly efficient transfection agents for delivery of siRNA or other nucleic acids to MSCs is an urgent task for the development of therapy based on these molecules. A comparative evaluation of five transfection agents showed that compounds based on cationic polymers were more efficient in delivering siRNA molecules than liposomes, while the cytotoxicity of all tested reagents was independent of their chemical structure. For two of the three transfection agents selected according to their efficiency and belonging to different classes, TurboFect and Lipofectamine® 3000, a moderate effect on cell viability was revealed. The results obtained allow us to recommend TurboFect and Lipofectamine® 3000 as highly efficient and relatively low-toxic agents for transfection of MSCs cultures. multipotent mesenchymal stromal cells, siRNA, transfection, lipofection, cationic lipids, cationic polymers, polyethyleneimine. The authors are grateful to staff of functional genomics laboratory of Research Centre for Medical Genetics Skoblova M.Yu. and Krivosheeva I.A., for technical and methodological assistance. The work was financially supported by the Ministry of Science and Higher Education of the Russian Federation within the state assignment for Research Centre for Medical Genetics.