Autism Spectrum Disorder (ASD) is one of the most prevalent neurodevelopmental disorders, reaching over 1% of individuals diagnosed worldwide. Its wide heterogeneity makes it particularly challenging to determine the ASD aetiology or to design a pharmacological treatment. While hundreds of ASD risk genes are being identified, no single one is found in more than 2% of diagnosed individuals, raising the need for a personalised approach. Cutting-edge genome editing tools are currently overcoming such limitations and can be used to correct disease mutations. Our aim is to address these limitations by creating a patient-derived hiPSCs models in which ASD aetiology can be investigated and potential gene therapy could be developed according to the mutation detected. First, a study with wild-type (WT) human induced pluripotent stem cells (hiPSCs) is being conducted by introducing an ASD risk mutation through precision gene editing technology, Prime Editing (PE); as PE efficiency can vary across different delivery methods, both plasmid DNA and mRNA are being optimised for the delivery of the PE machinery.  The knock-in (KI) hiPSCs will be differentiated into a whole-brain ASD-like three-dimensional (3D) model representing the neurodevelopment of an individual carrying an ASD risk mutation by using adjusted published protocols. Finally, a nanometric delivery system will be used to encapsulate the CRISPR/Cas9 machinery penetrating both the 2D and three-dimensional model, attempting to reverse the phenotype displayed in both models. This study could be applied to patient-derived hiPSCs which ultimately could set a precedent for evaluating gene therapy in ASD- derived in vitro models.