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Stem cell modeling of disease provides an unprecedented opportunity to fill in the gaps for developmental disorders. Boston Children's Hospital's Human Neuron Core (HNC) offers a new paradigm for disease modeling and preclinical drug screening in an academic setting. The mission of the core is to bridge the gap between the clinic and basic researchers and help establish human induced pluripotent stem cell (iPSC)-derived model systems for neurological disorders (NDDs) as well as provide support for pre-clinical research developing screens to identify novel therapeutics. One of the goals for HNC is to develop standard operating procedures for the generation of different types of neuronal cell lines. We first recruited, collected medical history, and reprogrammed peripheral blood mononuclear cells or fibroblasts from patients with various neurodevelopmental disorders to generate patient-specific iPSC lines. The iPSC lines were first characterized and then corrected to generate CRISPR corrected clones, as well as CRISPR non-corrected controls. HNC established a repository of 31 isogenic pairs of iPSC lines, two sex-matched parental control iPSC pairs, and one unmatched patient line from six monogenic NDDs. The six NDDs include Tuberous Sclerosis Complex (TSC2), PTEN Hamartoma Tumor Syndrome, KCNQ2 Developmental and Epileptic Encephalopathy, FOXG1 Syndrome, Phelan-McDermid Syndrome (SHANK3), and SETBP1 Haploinsufficiency Disorder. In addition to generating isogenic and familial control pairs from all 34 patients, clinical phenotyping data was collected to provide a basis for comparing future cellular phenotypes to determine if cellular models reflect clinical severity. This unique combination of cell lines and clinical phenotyping provides an opportunity to investigate the full potential of iPSC technology for drug discovery. We are currently establishing our Prime-Editing methodology to reduce off-target rate and ultimately expand the scope of genome editing on our iPSCs pool. The combination of iPSC-based model systems and CRISPR gene editing would pave the way for precision medicine and the clinical translation of genome editing-based therapies as well as drug screening to fit individual needs.