Genome engineering has become in the last few years more accessible thanks to the RNA programmable endonucleases such as the CRISPR-Cas9 system. However, using this editing technology in synthetic organs called ‘organoids’ is still very inefficient. This is due to the delivery methods used for the CRISPR-Cas9 machinery, which are mainly performed by electroporation of RNPs containing the CAS9-gRNA complex, a procedure toxic for the organoids. Here we describe the use of the ‘Nanoblade’ technology to accomplish genome editing in organoids. Nanoblades outperformed by far knockout levels achieved with other techniques used to date for delivery of the gene editing machinery. We reached up to 80% of gene knockout in organoids after treatment with nanoblades.  We achieved high-level nanoblade-mediated KO for the androgen receptor (AR) encoding gene and the cystic fibrosis transmembrane conductance regulator (CFTR) gene with single gRNA or dual gRNA containing nanoblades. Most importantly, in contrast to other gene editing methods, this was obtained without toxicity for the organoids. Moreover, it requires only four weeks to obtain stable lines of a gene KO in organoids and no obvious unwanted INDELS in off-target sites in the genome were detected. In conclusion, nanoblades simplify and allow rapid genome editing in organoids with little to no side-effects.