The field of epigenetics handles gene expression beyond the actual coding of the genome. Epigenetic markers regulate both which genes are expressed and to which extent. These markers differ between tissues and individuals and can change due to environmental factors. Additionally, epigenetic changes can be part of the problem in certain diseases, such as diabetes. Consequently, it is critical to have methods to study these changes in a controlled way. For this, injection (transfection) of molecules that can modify the epigenome and modulate gene expression has to be performed. The most commonly used transfection techniques today are lipid- and viral-based, which have inherent problems such as low efficiency and cytotoxicity. Using nanostraw electroporation (NS-EP) for transfecting cells results in a high transfection efficiency while maintaining high cell viability. Nanostraws (NS) are vertical hollow nanostructures protruding from a polycarbonate (PC) membrane, which allow direct intracellular access when cells are seeded on top of them. The cargo is in solution underneath the NS substrate. Mild electrical pulses are applied across the NS substrate, which open pores in the cell membrane and electrophoretically drive the cargo inside the cytosol (if charged). In this work, method optimization was carried out with a plasmid stained with an intercalating dye to enable direct analysis of the transfection results using flow cytometry. To ensure efficient transfection, different parameters were investigated, such as cell density, voltage, and straw length. NS-EP was then used to transfect beta cells with two plasmids to alter insulin gene expression epigenetically, one plasmid coding for a dead CAS9 and an effector domain, and the other for a single guide RNA. After transcription and translation, these molecules form a complex that can bind to a specific site on the genome, here the ins1-gene, and suppress its expression. Gene expression was analyzed using quantitative real-time PCR (qPCR). The results show that after optimization, this method successfully altered the expression of the target insulin gene.