Methods for modifying the genome of a Neural Stem Cell (NSC) are disclosed. Also, methods for differentiating NSCs into neurons and glia are described. NSCs are multipotent, self-renewing cells found in the central nervous system, capable of differentiating into neurons and glia. NSCs can be generated efficiently from pluripotent stem cells (PSCs) and have the capacity to differentiate into any neuronal or glial cell type of the central nervous system. Improvements in genome engineering of NSCs can potentially facilitate cellular replacement therapies for the treatment of neurodegenerative disorders. Recently, NIH investigators have developed a procedure to efficiently engineer NSCs through homologous recombination by introducing TAL effector nucleases (TALENs) and donor vectors. They have designed TALENs that efficiently generate double stranded breaks at two safe harbor loci (AAVS1 and CLYBL). These TALENs facilitate homologous recombination without silencing at these loci. The TALENs were delivered along with a DNA donor vector with a ubiquitous promoter driving expression of a cDNA using a nucleofector to get high transfection efficiencies. NSCs modified in this manner have therapeutic potential in treating neurodegenerative diseases. NSC lines engineered by this methodology as well as constructs and protocols for evaluation are also available.