In my Ph.D. project, I developed two novel gold-based nanoformulations of the Cas9 protein to improve the previously mentioned limitations. The first goal was to achieve efficient delivery of the Cas9 enzyme that could be potentially exploited for in vivo approaches. The protein was successfully conjugated onto the surface of 12nm gold spherical nanoparticles via affinity binding between the NTA-Ni²⁺ groups on the nanoparticle and the 6x His tag of the protein (AuNP-Cas9). The AuNP-Cas9 was able to cleave DNA in vitro and efficiently induce gene editing of the tyrosinase (tyr) gene in zebrafish. As hypothesized, the AuNP-Cas9 internalized in human melanoma cells spontaneously, and more importantly, entered the nucleus without the need for any further transfection method utilizing both passive and energy-dependent mechanisms for cellular uptake. Finally, the gene editing of the AuNP-Cas9 was validated in human melanoma cells. The second objective was to reduce the off-targets caused by the Cas9 in unintended positions by generating a photo-switchable system. For this reason, the nuclease activity of the Cas9 was replaced by a nanotransducer (NT) composed of a gold nanorod conjugated with the dCas9 protein (AuNR-dCas9). By designing two guides that pair at a short distance on opposite strands, it is possible to generate an NT dimer on the target DNA: the irradiation at the SPR wavelength of the dimer (but not the monomer) can be responsible for generating heating in a zeptoliter volume that can induce a thermal double-strand break (DSB). Firstly, it was shown that Au nanorods (NR) are able to induce localised heating, and the AuNR-dCas9 was designed in order to obtain a dimer of two NTs. The evaluation of the system was performed in zebrafish embryos and thus, an irradiation protocol was set up for zebrafish to irradiate them during the first stages of development. Finally, the zebrafish treated with the AuNR-dCas9 in complex with two different gRNAs to form a dimer were irradiated at 870 nm and their DNA presented large fragment deletions. This result indicated that upon irradiation the heat produced upon coupling of two gold nanorods induced DSBs leading to deletions. In conclusion, two nanoformulations were developed presenting different immediate applications. The first one is the AuNP-Cas9, which can be used as a gene editing technology with direct internalization in human cells without the need for transfection reagents which is one of the main disadvantages of the current technology. The second nanoformulation is the AuNR-dCas9 which is a nanotransducer exploiting the light activation of gold nanorods for the DSB induction, and by doing so, the activation of the gene editing process can be controlled in time and space, increasing the safety profile of the treatment.