Enabling customization of non-viral gene delivery systems for individual cell types by surface-induced mineralization

Delivering genes to mediate functions of cells is a crucial technology for both basic science and clinical applications. Though numerous non-viral gene delivery systems have been developed, the diversity of mammalian cells poses a great challenge to the material design. Here, we demonstrate that surface-induced mineralization represents a promising approach to systematically customize DNA delivery with respect to the characteristics of cells. We initially examined gene transfer in nine cell types derived from different tissues and organisms by surface-induced DNA-doped calcium carbonate nanocomposites derived from a library of mineral solutions. Subsequently, we correlated gene transfer efficiency with cellular uptake, pH responsiveness of nanocomposites, and phagosomal pH of individual cell types. Based on the correlation, we were able to optimize the DNA delivery to the cell types of interest. Surface-induced mineralization possesses great potential for customizing gene transfer in realizing gene- and cell-based therapy and probing functions of genes.