Metachromatic leukodystrophy (MLD) is a familial progressive neurologic dysfunction due to Arylsulfatase A (ASA) enzyme deficiency. The unfunctional enzyme cannot carry out its normal lysosomal process for sulfatides, therefore it leads neurodegeneration with a temporal decline. One of the propitious therapy options is through lentiviral-mediated autologous transplantation of Hematopoietic Stem Cells (HSC) that targets the primary nervous system manifestations; however insertional mutagenesis due to random is a risk that cannot be disregarded. Thus, we have chosen to study an approach that combines autologous HSC Transplantation (HSCT) with CRISPR/Cas9 system and non-integrating repair templates to ensure target integration and thereby create a safe gene therapy. Our approach provides guidance on non-viral gene-correction on HSC using Cas9 protein and single-strand DNA (ssDNA).