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 standard immortalized cell lines (adherent or suspension). Although optimized for HEK293 (human embryonic kidney 293 cells), this protocol is applicable to many other cell lines (A549, U2OS, HeLa, CHO, MCF-7). RNP delivery is accomplished using Lipofectamine™ CRISPRMAX™Transfection Reagent. 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 quality and consistently drive high editing efficiencies. Data that demonstrate editing efficiency in HEK293 cells are included.