This protocol describes how to deliver ribonucleoprotein (RNP) complexes that consist of purified Cas9 nuclease duplexed with chemically modified synthetic single guide RNA (sgRNA) to immortalized adherent or suspension cells. RNP delivery is accomplished using the Thermo Fisher NeonTM Transfection System. A reference for electroporation settings for a wide variety of cell types is included. A option for knock-in is included. Chemically modified sgRNAs are designed to resist exonucleases and innate intracellular immune cascades that can lead to cell death. Synthego chemically modified synthetic sgRNAs are of exceptional purity and consistently drive high editing frequencies.