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 induced pluripotent stem (iPS) cells derived from human fibroblasts. RNP delivery is accomplished using the Lonza 4D NucleofectorTM unit with 20 μl NucleocuvetteTM strips. Chemically modified sgRNAs are designed to resist exonucleases and innate intracellular immune cascades that can lead to cell death. Although primary cells can be challenging to transfect and manipulate, Synthego chemically modified synthetic sgRNAs are of exceptional purity and consistently drive high editing frequencies. Developed by researchers at Ludwig Maximilian University of Munich in conjunction with Synthego