{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T01:22:52Z","timestamp":1777598572200,"version":"3.51.4"},"reference-count":69,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2022,10,4]],"date-time":"2022-10-04T00:00:00Z","timestamp":1664841600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"Polish National Science Centre","doi-asserted-by":"publisher","award":["2015\/17\/B\/NZ4\/02669"],"award-info":[{"award-number":["2015\/17\/B\/NZ4\/02669"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004281","name":"Polish National Science Centre","doi-asserted-by":"publisher","award":["2019\/03\/X\/NZ3\/02139"],"award-info":[{"award-number":["2019\/03\/X\/NZ3\/02139"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Mutations in the SCN1A gene can cause a variety of phenotypes, ranging from mild forms, such as febrile seizures and generalized epilepsy with febrile seizures plus, to severe, such as Dravet and non-Dravet developmental epileptic encephalopathies. Until now, more than two thousand pathogenic variants of the SCN1A gene have been identified and different pathogenic mechanisms (loss vs. gain of function) described, but the precise molecular mechanisms responsible for the deficits exhibited by patients are not fully elucidated. Additionally, the phenotypic variability proves the involvement of other genetic factors in its final expression. This is the reason why animal models and cell line models used to explore the molecular pathology of SCN1A-related disorders are only of limited use. The results of studies based on such models cannot be directly translated to affected individuals because they do not address each patient\u2019s unique genetic background. The generation of functional neurons and glia for patient-derived iPSCs, together with the generation of isogenic controls using CRISPR\/Cas technology, and finally, the 3D brain organoid models, seem to be a good way to solve this problem. Here, we review SCN1A-related encephalopathies, as well as the stem cell models used to explore their molecular basis.<\/jats:p>","DOI":"10.3390\/cells11193119","type":"journal-article","created":{"date-parts":[[2022,10,8]],"date-time":"2022-10-08T01:52:21Z","timestamp":1665193941000},"page":"3119","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Concise Review: Stem Cell Models of SCN1A-Related Encephalopathies\u2014Current Perspective and Future Therapies"],"prefix":"10.3390","volume":"11","author":[{"given":"Valery","family":"Zayat","sequence":"first","affiliation":[{"name":"Department of Stem Cell Bioengineering, Mossakowski Medical Research Institute, Polish Academy of Sciences, 02106 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roza","family":"Szlendak","sequence":"additional","affiliation":[{"name":"Medical Genetics Department, Institute of Mother and Child, 01211 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7367-512X","authenticated-orcid":false,"given":"Dorota","family":"Hoffman-Zacharska","sequence":"additional","affiliation":[{"name":"Medical Genetics Department, Institute of Mother and Child, 01211 Warsaw, Poland"},{"name":"Faculty of Biology, Institute of Genetics and Biotechnology, University of Warsaw, 02106 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"a022426","DOI":"10.1101\/cshperspect.a022426","article-title":"Seizures and Epilepsy: An Overview for Neuroscientists","volume":"5","author":"Stafstrom","year":"2015","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.ejpn.2019.12.023","article-title":"Deciphering the Concepts behind \u201cEpileptic Encephalopathy\u201d and \u201cDevelopmental and Epileptic Encephalopathy\u201d","volume":"24","author":"Scheffer","year":"2020","journal-title":"Eur. J. Paediatr. Neurol. EJPN Off. J. Eur. Paediatr. Neurol. Soc."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1097\/WCO.0000000000000793","article-title":"What Are the Epileptic Encephalopathies?","volume":"33","author":"Trivisano","year":"2020","journal-title":"Curr. Opin. Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.1111\/epi.17241","article-title":"International League Against Epilepsy Classification and Definition of Epilepsy Syndromes with Onset in Childhood: Position Paper by the ILAE Task Force on Nosology and Definitions","volume":"63","author":"Specchio","year":"2022","journal-title":"Epilepsia"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1111\/epi.17239","article-title":"ILAE Classification and Definition of Epilepsy Syndromes with Onset in Neonates and Infants: Position Statement by the ILAE Task Force on Nosology and Definitions","volume":"63","author":"Zuberi","year":"2022","journal-title":"Epilepsia"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1007\/s11910-017-0720-7","article-title":"Epileptic Encephalopathies\u2014Clinical Syndromes and Pathophysiological Concepts","volume":"17","author":"Helbig","year":"2017","journal-title":"Curr. Neurol. Neurosci. Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1159\/000516388","article-title":"Voltage-Gated Sodium Channel \u03921 Gene: An Overview","volume":"85","author":"Liu","year":"2020","journal-title":"Hum. Hered."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1146\/annurev-pharmtox-011112-140232","article-title":"Sodium Channels, Inherited Epilepsy, and Antiepileptic Drugs","volume":"54","author":"Catterall","year":"2014","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"600050","DOI":"10.3389\/fneur.2021.600050","article-title":"Voltage Gated Sodium Channel Genes in Epilepsy: Mutations, Functional Studies, and Treatment Dimensions","volume":"12","author":"Ademuwagun","year":"2021","journal-title":"Front. Neurol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1038\/74159","article-title":"Mutations of SCN1A, Encoding a Neuronal Sodium Channel, in Two Families with GEFS+2","volume":"24","author":"Escayg","year":"2000","journal-title":"Nat. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1111\/epi.14074","article-title":"Diagnostic Outcomes for Genetic Testing of 70 Genes in 8565 Patients with Epilepsy and Neurodevelopmental Disorders","volume":"59","author":"Lindy","year":"2018","journal-title":"Epilepsia"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s10048-019-00598-x","article-title":"Customized Multigene Panels in Epilepsy: The Best Things Come in Small Packages","volume":"21","author":"Pellacani","year":"2020","journal-title":"Neurogenetics"},{"key":"ref_13","first-page":"e63","article-title":"Parental Mosaicism in Epilepsies Due to Alleged de Novo Variants","volume":"60","author":"Liebmann","year":"2019","journal-title":"Epilepsia"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1111\/epi.12123","article-title":"Divergent Effects of the T1174S SCN1A Mutation Associated with Seizures and Hemiplegic Migraine","volume":"54","author":"Labate","year":"2013","journal-title":"Epilepsia"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Brunklaus, A., Br\u00fcnger, T., Feng, T., Fons, C., Lehikoinen, A., Panagiotakaki, E., Vintan, M.-A., Symonds, J., Andrew, J., and Arzimanoglou, A. (2022). The Gain of Function SCN1A Disorder Spectrum: Novel Epilepsy Phenotypes and Therapeutic Implications. Brain J. Neurol., in press.","DOI":"10.1093\/brain\/awac210"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1002\/ana.25438","article-title":"SCN1A Gain of Function in Early Infantile Encephalopathy","volume":"85","author":"Berecki","year":"2019","journal-title":"Ann. Neurol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1212\/WNL.0000000000004331","article-title":"Not All SCN1A Epileptic Encephalopathies Are Dravet Syndrome: Early Profound Thr226Met Phenotype","volume":"89","author":"Sadleir","year":"2017","journal-title":"Neurology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1177\/0333102415608360","article-title":"Early-Onset Familial Hemiplegic Migraine Due to a Novel SCN1A Mutation","volume":"36","author":"Fan","year":"2016","journal-title":"Cephalalgia"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"232","DOI":"10.3389\/fnmol.2018.00232","article-title":"Gain of Function for the SCN1A\/HNav1.1-L1670W Mutation Responsible for Familial Hemiplegic Migraine","volume":"11","author":"Dhifallah","year":"2018","journal-title":"Front. Mol. Neurosci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1177\/0333102418788336","article-title":"Gain of Function of Sporadic\/Familial Hemiplegic Migraine-Causing SCN1A Mutations: Use of an Optimized CDNA","volume":"39","author":"Bertelli","year":"2019","journal-title":"Cephalalgia Int. J. Headache"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"602801","DOI":"10.3389\/fnmol.2020.602801","article-title":"Neuropathological Characterization of a Dravet Syndrome Knock-In Mouse Model Useful for Investigating Cannabinoid Treatments","volume":"13","author":"Satta","year":"2020","journal-title":"Front. Mol. Neurosci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"682767","DOI":"10.3389\/fphar.2021.682767","article-title":"Perampanel Reduces Hyperthermia-Induced Seizures in Dravet Syndrome Mouse Model","volume":"12","author":"Ho","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"ENEURO.0306-20.2021","DOI":"10.1523\/ENEURO.0306-20.2021","article-title":"Enhanced Synaptic Transmission in the Extended Amygdala and Altered Excitability in an Extended Amygdala to Brainstem Circuit in a Dravet Syndrome Mouse Model","volume":"8","author":"Yan","year":"2021","journal-title":"eNeuro"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.pjnns.2015.06.006","article-title":"From Focal Epilepsy to Dravet Syndrome\u2014Heterogeneity of the Phenotype Due to SCN1A Mutations of the p.Arg1596 Amino Acid Residue in the Nav1.1 Subunit","volume":"49","author":"Szczepanik","year":"2015","journal-title":"Neurol. Neurochir. Pol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"10288","DOI":"10.1038\/s41598-020-67215-y","article-title":"A Study among the Genotype, Functional Alternations, and Phenotype of 9 SCN1A Mutations in Epilepsy Patients","volume":"10","author":"Kluckova","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_26","first-page":"792","article-title":"Comprehensive Electrophysiological Analysis of SCN1A Arg1596Cys Mutation in a Family with Evolving Epi-Lepsy Phenotypes","volume":"28","author":"Nurowska","year":"2021","journal-title":"Eur. J. Neurol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s13073-020-00725-6","article-title":"Gene Family Information Facilitates Variant Interpretation and Identification of Disease-Associated Genes in Neurodevelopmental Disorders","volume":"12","author":"Lal","year":"2020","journal-title":"Genome Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1101\/gr.252601.119","article-title":"Identification of Pathogenic Variant Enriched Regions across Genes and Gene Families","volume":"30","author":"May","year":"2020","journal-title":"Genome Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/hdy.2017.14","article-title":"Contrasting Patterns of Population Structure and Gene Flow Facilitate Exploration of Connectivity in Two Widely Distributed Temperate Octocorals","volume":"119","author":"Holland","year":"2017","journal-title":"Heredity"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1111\/jnc.14134","article-title":"Models for Discovery of Targeted Therapy in Genetic Epileptic Encephalopathies","volume":"143","author":"Maljevic","year":"2017","journal-title":"J. Neurochem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1755","DOI":"10.1152\/jn.00824.2015","article-title":"Model Systems for Studying Cellular Mechanisms of SCN1A-Related Epilepsy","volume":"115","author":"Schutte","year":"2016","journal-title":"J. Neurophysiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"10022","DOI":"10.1523\/JNEUROSCI.2034-04.2004","article-title":"A Novel Epilepsy Mutation in the Sodium Channel SCN1A Identifies a Cytoplasmic Domain for Beta Subunit Interaction","volume":"24","author":"Spampanato","year":"2004","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"7481","DOI":"10.1523\/JNEUROSCI.21-19-07481.2001","article-title":"Functional Effects of Two Voltage-Gated Sodium Channel Mutations That Cause Generalized Epilepsy with Febrile Seizures plus Type 2","volume":"21","author":"Spampanato","year":"2001","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1016\/S0896-6273(02)00714-6","article-title":"Molecular Basis of an Inherited Epilepsy","volume":"34","author":"Lossin","year":"2002","journal-title":"Neuron"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1038\/nn1754","article-title":"Reduced Sodium Current in GABAergic Interneurons in a Mouse Model of Severe Myoclonic Epilepsy in Infancy","volume":"9","author":"Yu","year":"2006","journal-title":"Nat. Neurosci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1038\/nn.3934","article-title":"Animal Models in Epilepsy Research: Legacies and New Directions","volume":"18","author":"Grone","year":"2015","journal-title":"Nat. Neurosci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"7111","DOI":"10.1523\/JNEUROSCI.5193-09.2010","article-title":"Optogenetic Localization and Genetic Perturbation of Saccade-Generating Neurons in Zebrafish","volume":"30","author":"Schoonheim","year":"2010","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2410","DOI":"10.1038\/ncomms3410","article-title":"Drug Screening in Scn1a Zebrafish Mutant Identifies Clemizole as a Potential Dravet Syndrome Treatment","volume":"4","author":"Baraban","year":"2013","journal-title":"Nat. Commun."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1152\/jn.00135.2014","article-title":"Knock-in Model of Dravet Syndrome Reveals a Constitutive and Conditional Reduction in Sodium Current","volume":"112","author":"Schutte","year":"2014","journal-title":"J. Neurophysiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"14145","DOI":"10.1523\/JNEUROSCI.2932-12.2012","article-title":"A Knock-in Model of Human Epilepsy in Drosophila Reveals a Novel Cellular Mechanism Associated with Heat-Induced Seizure","volume":"32","author":"Sun","year":"2012","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Tapia, A., Giachello, C.N., Palomino-Sch\u00e4tzlein, M., Baines, R.A., and Galindo, M.I. (2021). Generation and Characterization of the Drosophila Melanogaster Paralytic Gene Knock-Out as a Model for Dravet Syndrome. Life, 11.","DOI":"10.3390\/life11111261"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1038\/jhg.2016.5","article-title":"Establishment of Isogenic IPSCs from an Individual with SCN1A Mutation Mosaicism as a Model for Investigating Neurocognitive Impairment in Dravet Syndrome","volume":"61","author":"Maeda","year":"2016","journal-title":"J. Hum. Genet."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"101523","DOI":"10.1016\/j.scr.2019.101523","article-title":"Generation of Three Human Induced Pluripotent Stem Cell (IPSC) Lines from Three Patients with Dravet Syndrome Carrying Distinct SCN1A Gene Mutations","volume":"39","author":"Schuster","year":"2019","journal-title":"Stem Cell Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"5B","DOI":"10.1002\/cpsc.15","article-title":"Comprehensive Protocols for CRISPR\/Cas9-Based Gene Editing in Human Pluripotent Stem Cells","volume":"38","author":"Santos","year":"2016","journal-title":"Curr. Protoc. Stem Cell Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1016\/j.stemcr.2022.02.008","article-title":"Homozygous Might Be Hemizygous: CRISPR\/Cas9 Editing in IPSCs Results in Detrimental on-Target Defects That Escape Standard Quality Controls","volume":"17","author":"Simkin","year":"2022","journal-title":"Stem Cell Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4241","DOI":"10.1093\/hmg\/ddt275","article-title":"Modeling Dravet Syndrome Using Induced Pluripotent Stem Cells (IPSCs) and Directly Converted Neurons","volume":"22","author":"Jiao","year":"2013","journal-title":"Hum. Mol. Genet."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"101785","DOI":"10.1016\/j.scr.2020.101785","article-title":"Generation of IPSC Line (USTCi001-A) from Human Skin Fibroblasts of a Patient with Epilepsy","volume":"45","author":"Zhao","year":"2020","journal-title":"Stem Cell Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"101864","DOI":"10.1016\/j.scr.2020.101864","article-title":"Generation of Corrected-HiPSC (USTCi001-A-1) from Epilepsy Patient IPSCs Using TALEN-Mediated Editing of the SCN1A Gene","volume":"46","author":"Zhao","year":"2020","journal-title":"Stem Cell Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"102003","DOI":"10.1016\/j.scr.2020.102003","article-title":"Generation of a TdTomato-GAD67 Reporter Human Epilepsia Mutation Induced Pluripotent Stem Cell Line, USTCi001-A-2, Using CRISPR\/Cas9 Editing","volume":"48","author":"Zhao","year":"2020","journal-title":"Stem Cell Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e703","DOI":"10.1038\/tp.2015.203","article-title":"CRISPR\/Cas9 Facilitates Investigation of Neural Circuit Disease Using Human IPSCs: Mechanism of Epilepsy Caused by an SCN1A Loss-of-Function Mutation","volume":"6","author":"Liu","year":"2016","journal-title":"Transl. Psychiatry"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1007\/s12035-021-02633-1","article-title":"Ameliorating Effect of Umbilical Cord Mesenchymal Stem Cells in a Human Induced Pluripotent Stem Cell Model of Dravet Syndrome","volume":"59","author":"Zhao","year":"2022","journal-title":"Mol. Neurobiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"102058","DOI":"10.1016\/j.scr.2020.102058","article-title":"A Heterozygous SCN1A (c.A5768G\/+) Mutant Human Induced Pluripotent Stem Cell Line (USTCi002-A) Generated Using TALEN-Mediated Precise Gene Editing","volume":"49","author":"Zhao","year":"2020","journal-title":"Stem Cell Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"104627","DOI":"10.1016\/j.nbd.2019.104627","article-title":"Comparisons of Dual Isogenic Human IPSC Pairs Identify Functional Alterations Directly Caused by an Epilepsy Associated SCN1A Mutation","volume":"134","author":"Xie","year":"2020","journal-title":"Neurobiol. Dis."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"102083","DOI":"10.1016\/j.scr.2020.102083","article-title":"Generation of IPSC Lines from Two Patients Affected by Febrile Seizure Due to Inherited Missense Mutation in SCN1A Gene","volume":"49","author":"Scalise","year":"2020","journal-title":"Stem Cell Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1002\/ana.23897","article-title":"Dravet Syndrome Patient-Derived Neurons Suggest a Novel Epilepsy Mechanism","volume":"74","author":"Liu","year":"2013","journal-title":"Ann. Neurol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/1756-6606-6-19","article-title":"A Human Dravet Syndrome Model from Patient Induced Pluripotent Stem Cells","volume":"6","author":"Higurashi","year":"2013","journal-title":"Mol. Brain"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"5404","DOI":"10.1038\/srep05404","article-title":"Generation of the SCN1A Epilepsy Mutation in HiPS Cells Using the TALEN Technique","volume":"4","author":"Chen","year":"2014","journal-title":"Sci. Rep."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e13073","DOI":"10.7554\/eLife.13073","article-title":"A Deleterious Nav1.1 Mutation Selectively Impairs Telencephalic Inhibitory Neurons Derived from Dravet Syndrome Patients","volume":"5","author":"Sun","year":"2016","journal-title":"eLife"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.braindev.2017.12.002","article-title":"Differential Effects on Sodium Current Impairments by Distinct SCN1A Mutations in GABAergic Neurons Derived from Dravet Syndrome Patients","volume":"40","author":"Kim","year":"2018","journal-title":"Brain Dev."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.scr.2018.01.036","article-title":"Generation of D1-1 TALEN Isogenic Control Cell Line from Dravet Syndrome Patient IPSCs Using TALEN-Mediated Editing of the SCN1A Gene","volume":"28","author":"Tanaka","year":"2018","journal-title":"Stem Cell Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.scr.2018.06.008","article-title":"Establishment of a Human Induced Stem Cell Line (FUi002-A) from Dravet Syndrome Patient Carrying Heterozygous R1525X Mutation in SCN1A Gene","volume":"31","author":"Tanaka","year":"2018","journal-title":"Stem Cell Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1016\/j.stemcr.2018.07.012","article-title":"Channelopathy as a SUDEP Biomarker in Dravet Syndrome Patient-Derived Cardiac Myocytes","volume":"11","author":"Frasier","year":"2018","journal-title":"Stem Cell Rep."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"104583","DOI":"10.1016\/j.nbd.2019.104583","article-title":"Transcriptomes of Dravet Syndrome IPSC Derived GABAergic Cells Reveal Dysregulated Pathways for Chromatin Remodeling and Neurodevelopment","volume":"132","author":"Schuster","year":"2019","journal-title":"Neurobiol. Dis."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"101857","DOI":"10.1016\/j.scr.2020.101857","article-title":"Establishment of Human Induced Pluripotent Stem Cells Derived from Skin Cells of a Patient with Dravet Syndrome","volume":"47","author":"Kimura","year":"2020","journal-title":"Stem Cell Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"102452","DOI":"10.1016\/j.scr.2021.102452","article-title":"Generation of SCN1A Knock out Induced Pluripotent Stem Cell (IPSC) Line","volume":"55","author":"Shan","year":"2021","journal-title":"Stem Cell Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.eplepsyres.2016.10.006","article-title":"Mortality in Dravet Syndrome","volume":"128","author":"Cooper","year":"2016","journal-title":"Epilepsy Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1113\/jphysiol.2014.278259","article-title":"Contribution of Sodium Channel Neuronal Isoform Nav1.1 to Late Sodium Current in Ventricular Myocytes from Failing Hearts","volume":"593","author":"Mishra","year":"2015","journal-title":"J. Physiol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1007\/s11948-015-9693-6","article-title":"Some Ethical Concerns About Human Induced Pluripotent Stem Cells","volume":"22","author":"Zheng","year":"2016","journal-title":"Sci. Eng. Ethics"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Nahmad, A.D., Reuveni, E., Goldschmidt, E., Tenne, T., Liberman, M., Horovitz-Fried, M., Khosravi, R., Kobo, H., Reinstein, E., and Madi, A. (2022). Frequent Aneuploidy in Primary Human T Cells after CRISPR\u2013Cas9 Cleavage. Nat. Biotechnol., 1\u20137.","DOI":"10.1101\/2021.08.20.457092"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/19\/3119\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:46:14Z","timestamp":1760143574000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/19\/3119"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,4]]},"references-count":69,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["cells11193119"],"URL":"https:\/\/doi.org\/10.3390\/cells11193119","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,4]]}}}