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 cells or suspension cells. RNP delivery is accomplished using the Lonza 4D NucleofectorTM\u00a0unit with 16-well NucleocuvetteTM\u00a0Strips. 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\u00a0exceptional\u00a0purity and consistently drive high editing efficiencies.