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It has been suggested that microinjection of sgRNA and Cas9 ribonucleoprotein complexes may reduce mosaicism and allelic complexity by bypassing the requirement for Cas9 translation and sgRNA–Cas9 complex formation in embryos19, 20.

Non-parametric two-tailed Kolmogorov–Smirnov test; NS, not significant. d, Kaplan–Meier survival curve of human embryos following microinjection of Cas9 protein or sgRNA2b–Cas9 ribonucleoprotein complex.

All other embryos were microinjected with the sgRNA2b–Cas9 ribonucleoprotein complex.

A representative graph indicating aneuploidy in embryos following Cas9 protein and sgRNA2b–Cas9 ribonucleoprotein complex microinjection. c, Phase-contrast images of starting blastocysts and blastocysts that developed following microinjection of the sgRNA2b–Cas9 complex compared to Cas9 protein-injected controls.

Data are mean ± s.d. f, Quantification of proportions of OCT4-null, mosaic or wild-type mouse blastocysts after microinjection of the sgRNA2b–Cas9 ribonucleoprotein complex at concentrations indicated.