{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:00:43Z","timestamp":1792803643348,"version":"4.5.0"},"reference-count":131,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,1,3]],"date-time":"2024-01-03T00:00:00Z","timestamp":1704240000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Helen DeVos Children\u2019s Hospital","id":[{"id":"https:\/\/ror.org\/03bk8p931","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Michigan State University","id":[{"id":"https:\/\/ror.org\/05hs6h993","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Gerber Foundation","id":[{"id":"https:\/\/ror.org\/03ggcx620","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["BioTech"],"abstract":"<jats:p>Gene therapy holds promise as a life-changing option for individuals with genetic variants that give rise to disease. FDA-approved gene therapies for Spinal Muscular Atrophy (SMA), cerebral adrenoleukodystrophy, \u03b2-Thalassemia, hemophilia A\/B, retinal dystrophy, and Duchenne Muscular Dystrophy have generated buzz around the ability to change the course of genetic syndromes. However, this excitement risks over-expansion into areas of genetic disease that may not fit the current state of gene therapy. While in situ (targeted to an area) and ex vivo (removal of cells, delivery, and administration of cells) approaches show promise, they have a limited target ability. Broader in vivo gene therapy trials have shown various continued challenges, including immune response, use of immune suppressants correlating to secondary infections, unknown outcomes of overexpression, and challenges in driving tissue-specific corrections. Viral delivery systems can be associated with adverse outcomes such as hepatotoxicity and lethality if uncontrolled. In some cases, these risks are far outweighed by the potentially lethal syndromes for which these systems are being developed. Therefore, it is critical to evaluate the field of genetic diseases to perform cost\u2013benefit analyses for gene therapy. In this work, we present the current state while setting forth tools and resources to guide informed directions to avoid foreseeable issues in gene therapy that could prevent the field from continued success.<\/jats:p>","DOI":"10.3390\/biotech13010001","type":"journal-article","created":{"date-parts":[[2024,1,3]],"date-time":"2024-01-03T03:18:07Z","timestamp":1704251887000},"page":"1","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Gene Therapy for Genetic Syndromes: Understanding the Current State to Guide Future Care"],"prefix":"10.3390","volume":"13","author":[{"given":"Marian L.","family":"Henderson","sequence":"first","affiliation":[{"name":"The Department of Biology, Calvin University, Grand Rapids, MI 49546, USA"},{"name":"Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, Grand Rapids, MI 48824, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob K.","family":"Zieba","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, Grand Rapids, MI 48824, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaopeng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, Grand Rapids, MI 48824, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel B.","family":"Campbell","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, Grand Rapids, MI 48824, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, Grand Rapids, MI 48824, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1876-5936","authenticated-orcid":false,"given":"Daniel L.","family":"Vogt","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, Grand Rapids, MI 48824, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caleb P.","family":"Bupp","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, Grand Rapids, MI 48824, USA"},{"name":"Medical Genetics, Corewell Health, Grand Rapids, MI 49503, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvonne M.","family":"Edgerly","sequence":"additional","affiliation":[{"name":"Office of Research, Corewell Health, Grand Rapids, MI 49503, 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and Human Development, College of Human Medicine, Michigan State University, Grand Rapids, MI 48824, USA"},{"name":"Office of Research, Corewell Health, Grand Rapids, MI 49503, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jena M.","family":"Krueger","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, Grand Rapids, MI 48824, USA"},{"name":"Department of Neurology, Helen DeVos Children\u2019s Hospital, Corewell Health, Grand Rapids, MI 49503, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.gene.2013.03.137","article-title":"History of Gene Therapy","volume":"525","author":"Wirth","year":"2013","journal-title":"Gene"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"eaan4672","DOI":"10.1126\/science.aan4672","article-title":"Gene Therapy Comes of Age","volume":"359","author":"Dunbar","year":"2018","journal-title":"Science"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/S0014-5793(97)00311-6","article-title":"The Packaging Capacity of Adeno-Associated Virus (AAV) and the Potential for Wild-Type-Plus AAV Gene Therapy Vectors","volume":"407","author":"Hermonat","year":"1997","journal-title":"FEBS Lett."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.ijpharm.2013.11.041","article-title":"Gene Therapy and DNA Delivery Systems","volume":"459","author":"Ibraheem","year":"2014","journal-title":"Int. J. Pharm."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jconrel.2003.09.013","article-title":"An Overview of Current Delivery Systems in Cancer Gene Therapy","volume":"94","year":"2004","journal-title":"J. Control. Release"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1038\/s41573-019-0012-9","article-title":"Adeno-Associated Virus Vector as a Platform for Gene Therapy Delivery","volume":"18","author":"Wang","year":"2019","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1211\/0022357011776603","article-title":"The Challenge of Gene Therapy and DNA Delivery","volume":"53","author":"Phillips","year":"2001","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1126\/science.6093246","article-title":"Prospects for Human Gene Therapy","volume":"226","author":"Anderson","year":"1984","journal-title":"Science"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1056\/NEJM199008303230904","article-title":"Gene Transfer into Humans\u2014Immunotherapy of Patients with Advanced Melanoma, Using Tumor-Infiltrating Lymphocytes Modified by Retroviral Gene Transduction","volume":"323","author":"Rosenberg","year":"1990","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1186\/s13023-022-02299-5","article-title":"The National Economic Burden of Rare Disease in the United States in 2019","volume":"17","author":"Yang","year":"2022","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2711","DOI":"10.1111\/apa.15974","article-title":"Progress, Challenges and Global Approaches to Rare Diseases","volume":"110","author":"Groft","year":"2021","journal-title":"Acta Paediatr."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2039","DOI":"10.1016\/S0140-6736(08)60872-7","article-title":"Why Rare Diseases Are an Important Medical and Social Issue","volume":"371","author":"Schieppati","year":"2008","journal-title":"Lancet"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1002\/humu.22982","article-title":"Gene Variant Databases and Sharing: Creating a Global Genomic Variant Database for Personalized Medicine","volume":"37","author":"Bean","year":"2016","journal-title":"Hum. Mutat."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1016\/j.ajhg.2017.04.003","article-title":"International Cooperation to Enable the Diagnosis of All Rare Genetic Diseases","volume":"100","author":"Boycott","year":"2017","journal-title":"Am. J. Hum. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1660","DOI":"10.1002\/humu.23607","article-title":"The Value of Genomic Variant ClinVar Submissions from Clinical Providers: Beyond the Addition of Novel Variants","volume":"39","author":"Wain","year":"2018","journal-title":"Hum. Mutat."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1111\/cts.12500","article-title":"Future of Rare Diseases Research 2017-2027: An IRDiRC Perspective","volume":"11","author":"Austin","year":"2018","journal-title":"Clin. Transl. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1038\/s41431-017-0008-z","article-title":"The International Rare Diseases Research Consortium: Policies and Guidelines to Maximize Impact","volume":"25","author":"Jonker","year":"2017","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1038\/gt.2017.29","article-title":"The Importance of International Collaboration for Rare Diseases Research: A European Perspective","volume":"24","author":"Julkowska","year":"2017","journal-title":"Gene Ther."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1111\/j.1651-2227.2012.02705.x","article-title":"The Need for Worldwide Policy and Action Plans for Rare Diseases","volume":"101","author":"Forman","year":"2012","journal-title":"Acta Paediatr."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1016\/j.gim.2021.11.020","article-title":"Genome Sequencing as a First-Line Diagnostic Test for Hospitalized Infants","volume":"24","author":"Bowling","year":"2022","journal-title":"Genet. Med."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Bupp, C.P., Ames, E.G., Arenchild, M.K., Caylor, S., Dimmock, D.P., Fakhoury, J.D., Karna, P., Lehman, A., Meghea, C.I., and Misra, V. (2023). Breaking Barriers to Rapid Whole Genome Sequencing in Pediatrics: Michigan\u2019s Project Baby Deer. Children, 10.","DOI":"10.3390\/children10010106"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1152\/physiolgenomics.00046.2018","article-title":"Genome Sequencing in the Clinic: The Past, Present, and Future of Genomic Medicine","volume":"50","author":"Prokop","year":"2018","journal-title":"Physiol. Genom."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3303","DOI":"10.1002\/cphy.c210012","article-title":"Computational and Experimental Analysis of Genetic Variants","volume":"12","author":"Prokop","year":"2022","journal-title":"Compr. Physiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1007\/s00894-017-3258-3","article-title":"Molecular Modeling in the Age of Clinical Genomics, the Enterprise of the next Generation","volume":"23","author":"Prokop","year":"2017","journal-title":"J. Mol. Model."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e67097","DOI":"10.7554\/eLife.67097","article-title":"Repurposing Eflornithine to Treat a Patient with a Rare ODC1 Gain-of-Function Variant Disease","volume":"10","author":"Rajasekaran","year":"2021","journal-title":"Elife"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Stainier, D.Y.R., Raz, E., Lawson, N.D., Ekker, S.C., Burdine, R.D., Eisen, J.S., Ingham, P.W., Schulte-Merker, S., Yelon, D., and Weinstein, B.M. (2017). Guidelines for Morpholino Use in Zebrafish. PLoS Genet., 13.","DOI":"10.1371\/journal.pgen.1007000"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/S0091-679X(08)60279-4","article-title":"Fertilization of Cultured Xenopus Oocytes and Use in Studies of Maternally Inherited Molecules","volume":"36","author":"Heasman","year":"1991","journal-title":"Methods Cell Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1006\/dbio.2001.0565","article-title":"Morpholino Oligos: Making Sense of Antisense?","volume":"243","author":"Heasman","year":"2002","journal-title":"Dev. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1038\/79951","article-title":"Effective Targeted Gene \u201cknockdown\u201d in Zebrafish","volume":"26","author":"Nasevicius","year":"2000","journal-title":"Nat. Genet."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1089\/zeb.2008.0555","article-title":"A Primer for Morpholino Use in Zebrafish","volume":"6","author":"Bill","year":"2009","journal-title":"Zebrafish"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Robu, M.E., Larson, J.D., Nasevicius, A., Beiraghi, S., Brenner, C., Farber, S.A., and Ekker, S.C. (2007). P53 Activation by Knockdown Technologies. PLoS Genet., 3.","DOI":"10.1371\/journal.pgen.0030078"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1892","DOI":"10.1073\/pnas.0308698100","article-title":"Short Interfering RNAs Can Induce Unexpected and Divergent Changes in the Levels of Untargeted Proteins in Mammalian Cells","volume":"101","author":"Scacheri","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"651","DOI":"10.2174\/156802607780487740","article-title":"Morpholino, siRNA, and S-DNA Compared: Impact of Structure and Mechanism of Action on off-Target Effects and Sequence Specificity","volume":"7","author":"Summerton","year":"2007","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.1242\/dev.001115","article-title":"Controlling Morpholino Experiments: Don\u2019t Stop Making Antisense","volume":"135","author":"Eisen","year":"2008","journal-title":"Development"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1093\/bfgp\/elr021","article-title":"Lessons from Morpholino-Based Screening in Zebrafish","volume":"10","author":"Bedell","year":"2011","journal-title":"Brief. Funct. Genom."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1525","DOI":"10.1681\/ASN.2017080856","article-title":"Characterization of Coding\/Noncoding Variants for SHROOM3 in Patients with CKD","volume":"29","author":"Prokop","year":"2018","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3103","DOI":"10.1242\/dev.112003","article-title":"Out with the Old, in with the New: Reassessing Morpholino Knockdowns in Light of Genome Editing Technology","volume":"141","author":"Stainier","year":"2014","journal-title":"Development"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1038\/nrd3025","article-title":"The Future of Drug Development: Advancing Clinical Trial Design","volume":"8","author":"Orloff","year":"2009","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1089\/humc.2018.201","article-title":"The Landscape of Cellular and Gene Therapy Products: Authorization, Discontinuations, and Cost","volume":"30","author":"Shukla","year":"2019","journal-title":"Hum. Gene Ther. Clin. Dev."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1002\/(SICI)1098-1004(200003)15:3<228::AID-HUMU3>3.0.CO;2-9","article-title":"An Update of the Mutation Spectrum of the Survival Motor Neuron Gene (SMN1) in Autosomal Recessive Spinal Muscular Atrophy (SMA)","volume":"15","author":"Wirth","year":"2000","journal-title":"Hum. Mutat."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1038\/s41436-020-0824-3","article-title":"Implementation of Population-Based Newborn Screening Reveals Low Incidence of Spinal Muscular Atrophy","volume":"22","author":"Kay","year":"2020","journal-title":"Genet. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/S1474-4422(21)00001-6","article-title":"Onasemnogene Abeparvovec Gene Therapy for Symptomatic Infantile-Onset Spinal Muscular Atrophy in Patients with Two Copies of SMN2 (STR1VE): An Open-Label, Single-Arm, Multicentre, Phase 3 Trial","volume":"20","author":"Day","year":"2021","journal-title":"Lancet Neurol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1038\/s41591-022-01866-4","article-title":"Onasemnogene Abeparvovec for Presymptomatic Infants with Two Copies of SMN2 at Risk for Spinal Muscular Atrophy Type 1: The Phase III SPR1NT Trial","volume":"28","author":"Strauss","year":"2022","journal-title":"Nat. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"xxv","DOI":"10.1016\/j.ajo.2018.08.038","article-title":"The Blunt End: Surgical Challenges of Gene Therapy for Inherited Retinal Diseases","volume":"196","author":"Davis","year":"2018","journal-title":"Am. J. Ophthalmol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1630","DOI":"10.1056\/NEJMoa1700554","article-title":"Hematopoietic Stem-Cell Gene Therapy for Cerebral Adrenoleukodystrophy","volume":"377","author":"Eichler","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1056\/NEJMoa2113206","article-title":"Betibeglogene Autotemcel Gene Therapy for Non-\u03920\/\u03920 Genotype \u03b2-Thalassemia","volume":"386","author":"Locatelli","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"662838","DOI":"10.3389\/fneur.2021.662838","article-title":"Intravitreal Gene Therapy vs. Natural History in Patients With Leber Hereditary Optic Neuropathy Carrying the m.11778G>A ND4 Mutation: Systematic Review and Indirect Comparison","volume":"12","author":"Newman","year":"2021","journal-title":"Front. Neurol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1089\/104303401753153956","article-title":"A Phase I Study of Aerosolized Administration of tgAAVCF to Cystic Fibrosis Subjects with Mild Lung Disease","volume":"12","author":"Aitken","year":"2001","journal-title":"Hum. Gene Ther."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1378\/chest.125.2.509","article-title":"Repeated Adeno-Associated Virus Serotype 2 Aerosol-Mediated Cystic Fibrosis Transmembrane Regulator Gene Transfer to the Lungs of Patients with Cystic Fibrosis: A Multicenter, Double-Blind, Placebo-Controlled Trial","volume":"125","author":"Moss","year":"2004","journal-title":"Chest"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1089\/hum.2007.022","article-title":"Repeated Aerosolized AAV-CFTR for Treatment of Cystic Fibrosis: A Randomized Placebo-Controlled Phase 2B Trial","volume":"18","author":"Moss","year":"2007","journal-title":"Hum. Gene Ther."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1016\/S0140-6736(17)31868-8","article-title":"Efficacy and Safety of Voretigene Neparvovec (AAV2-hRPE65v2) in Patients with RPE65-Mediated Inherited Retinal Dystrophy: A Randomised, Controlled, Open-Label, Phase 3 Trial","volume":"390","author":"Russell","year":"2017","journal-title":"Lancet"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1056\/NEJMoa2113708","article-title":"Valoctocogene Roxaparvovec Gene Therapy for Hemophilia A","volume":"386","author":"Ozelo","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1038\/gt.2017.59","article-title":"Spinraza-a Rare Disease Success Story","volume":"24","author":"Prakash","year":"2017","journal-title":"Gene Ther."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1056\/NEJMoa1710504","article-title":"Nusinersen versus Sham Control in Later-Onset Spinal Muscular Atrophy","volume":"378","author":"Mercuri","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1056\/NEJMoa1908639","article-title":"Elexacaftor-Tezacaftor-Ivacaftor for Cystic Fibrosis with a Single Phe508del Allele","volume":"381","author":"Middleton","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1056\/NEJMoa2100665","article-title":"Triple Therapy for Cystic Fibrosis Phe508del-Gating and -Residual Function Genotypes","volume":"385","author":"Barry","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"D789","DOI":"10.1093\/nar\/gku1205","article-title":"OMIM.Org: Online Mendelian Inheritance in Man (OMIM\u00ae), an Online Catalog of Human Genes and Genetic Disorders","volume":"43","author":"Amberger","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"(2015). UniProt Consortium UniProt: A Hub for Protein Information. Nucleic Acids Res., 43, D204\u2013D212.","DOI":"10.1093\/nar\/gku989"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1038\/nbt1210-1248","article-title":"Towards a Knowledge-Based Human Protein Atlas","volume":"28","author":"Uhlen","year":"2010","journal-title":"Nat. Biotechnol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1038\/ng.3901","article-title":"Disease Model Discovery from 3,328 Gene Knockouts by The International Mouse Phenotyping Consortium","volume":"49","author":"Meehan","year":"2017","journal-title":"Nat. Genet."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"D862","DOI":"10.1093\/nar\/gkv1222","article-title":"ClinVar: Public Archive of Interpretations of Clinically Relevant Variants","volume":"44","author":"Landrum","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1007\/BF00210632","article-title":"Cell Type Specific and Inducible Promoters for Vectors in Gene Therapy as an Approach for Cell Targeting","volume":"74","author":"Walther","year":"1996","journal-title":"J. Mol. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"4637","DOI":"10.1242\/dev.01350","article-title":"Neural Crest Cell Plasticity and Its Limits","volume":"131","author":"Creuzet","year":"2004","journal-title":"Development"},{"key":"ref_64","first-page":"a006169","article-title":"Autosomal Recessive LRP1-Related Syndrome Featuring Cardiopulmonary Dysfunction, Bone Dysmorphology, and Corneal Clouding","volume":"8","author":"Mark","year":"2022","journal-title":"Cold Spring Harb. Mol. Case Stud."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e118","DOI":"10.1212\/NXG.0000000000000118","article-title":"Germline and Somatic Mutations in the MTOR Gene in Focal Cortical Dysplasia and Epilepsy","volume":"2","author":"Weckhuysen","year":"2016","journal-title":"Neurol. Genet."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2065","DOI":"10.1016\/j.gim.2022.07.005","article-title":"Heterozygous Variants in MYH10 Associated with Neurodevelopmental Disorders and Congenital Anomalies with Evidence for Primary Cilia-Dependent Defects in Hedgehog Signaling","volume":"24","author":"Holtz","year":"2022","journal-title":"Genet. Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"a005496","DOI":"10.1101\/mcs.a005496","article-title":"Rapid Whole-Genome Sequencing Identifies a Homozygous Novel Variant, His540Arg, in HSD17B4 Resulting in D-Bifunctional Protein Deficiency Disorder Diagnosis","volume":"6","author":"Savage","year":"2020","journal-title":"Cold Spring Harb. Mol. Case Stud."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Cook, T.W., Wilstermann, A.M., Mitchell, J.T., Arnold, N.E., Rajasekaran, S., Bupp, C.P., and Prokop, J.W. (2023). Understanding Insulin in the Age of Precision Medicine and Big Data: Under-Explored Nature of Genomics. Biomolecules, 13.","DOI":"10.3390\/biom13020257"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"a005868","DOI":"10.1101\/mcs.a005868","article-title":"NAA10 Variant in 38-Week-Gestation Male Patient: A Case Study","volume":"6","author":"Afrin","year":"2020","journal-title":"Cold Spring Harb. Mol. Case Stud."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Underwood, A., Rasicci, D.T., Hinds, D., Mitchell, J.T., Zieba, J.K., Mills, J., Arnold, N.E., Cook, T.W., Moustaqil, M., and Gambin, Y. (2023). Evolutionary Landscape of SOX Genes to Inform Genotype-to-Phenotype Relationships. Genes, 14.","DOI":"10.3390\/genes14010222"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1007\/s00439-018-1887-y","article-title":"De Novo Mutations in MED13, a Component of the Mediator Complex, Are Associated with a Novel Neurodevelopmental Disorder","volume":"137","author":"Hiatt","year":"2018","journal-title":"Hum. Genet."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"GTEx Consortium (2020). The GTEx Consortium Atlas of Genetic Regulatory Effects across Human Tissues. Science, 369, 1318\u20131330.","DOI":"10.1126\/science.aaz1776"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Das, A.S., Sherry, E.C., Vaughan, R.M., Henderson, M.L., Zieba, J., Uhl, K.L., Koehn, O., Bupp, C.P., Rajasekaran, S., and Li, X. (2022). The Complex, Dynamic SpliceOme of the Small GTPase Transcripts Altered by Technique, Sex, Genetics, Tissue Specificity, and RNA Base Editing. Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.1033695"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"2235","DOI":"10.1056\/NEJMsr1406261","article-title":"ClinGen\u2014The Clinical Genome Resource","volume":"372","author":"Rehm","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1038\/s41434-019-0080-9","article-title":"Feasibility of Using NF1-GRD and AAV for Gene Replacement Therapy in NF1-Associated Tumors","volume":"26","author":"Bai","year":"2019","journal-title":"Gene Ther."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"D1056","DOI":"10.1093\/nar\/gky1133","article-title":"Open Targets Platform: New Developments and Updates Two Years On","volume":"47","author":"Pierleoni","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Nayerossadat, N., Maedeh, T., and Ali, P.A. (2012). Viral and Nonviral Delivery Systems for Gene Delivery. Adv. Biomed. Res., 1.","DOI":"10.4103\/2277-9175.98152"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Wang, Y., Zhang, R., Tang, L., and Yang, L. (2022). Nonviral Delivery Systems of mRNA Vaccines for Cancer Gene Therapy. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14030512"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1016\/j.ymthe.2023.01.021","article-title":"Extracellular Vesicles: The next Generation in Gene Therapy Delivery","volume":"31","author":"Cecchin","year":"2023","journal-title":"Mol. Ther."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"120375","DOI":"10.1016\/j.lfs.2022.120375","article-title":"Gene Therapy: Comprehensive Overview and Therapeutic Applications","volume":"294","author":"Sayed","year":"2022","journal-title":"Life Sci."},{"key":"ref_81","first-page":"495","article-title":"Human Gene Therapy: Novel Approaches to Improve the Current Gene Delivery Systems","volume":"21","author":"Cucchiarini","year":"2016","journal-title":"Discov. Med."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1007\/s00439-020-02211-w","article-title":"Genomic, Transcriptomic, and Protein Landscape Profile of CFTR and Cystic Fibrosis","volume":"140","author":"Sanders","year":"2021","journal-title":"Hum. Genet."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Keswani, S.G., Balaji, S., Le, L., Leung, A., Katz, A.B., Lim, F.-Y., Habli, M., Jones, H.N., Wilson, J.M., and Crombleholme, T.M. (2012). Pseudotyped AAV Vector-Mediated Gene Transfer in a Human Fetal Trachea Xenograft Model: Implications for in Utero Gene Therapy for Cystic Fibrosis. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0043633"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1038\/mt.2008.261","article-title":"Transduction Efficiencies of Novel AAV Vectors in Mouse Airway Epithelium In Vivo and Human Ciliated Airway Epithelium In Vitro","volume":"17","author":"Limberis","year":"2009","journal-title":"Mol. Ther."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"6085","DOI":"10.1128\/JVI.73.7.6085-6088.1999","article-title":"Transduction of Well-Differentiated Airway Epithelium by Recombinant Adeno-Associated Virus Is Limited by Vector Entry","volume":"73","author":"Bals","year":"1999","journal-title":"J. Virol."},{"key":"ref_86","first-page":"832","article-title":"Functional Characterization of a Recombinant Adeno-Associated Virus 5-Pseudotyped Cystic Fibrosis Transmembrane Conductance Regulator Vector","volume":"15","author":"Sirninger","year":"2004","journal-title":"Hum. Gene Ther."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"3852","DOI":"10.1128\/JVI.74.8.3852-3858.2000","article-title":"Adeno-Associated Virus Type 5 (AAV5) but Not AAV2 Binds to the Apical Surfaces of Airway Epithelia and Facilitates Gene Transfer","volume":"74","author":"Zabner","year":"2000","journal-title":"J. Virol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1038\/sj.mt.6300059","article-title":"Expression of a Truncated Cystic Fibrosis Transmembrane Conductance Regulator with an AAV5-Pseudotyped Vector in Primates","volume":"15","author":"Fischer","year":"2007","journal-title":"Mol. Ther."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1089\/hum.2008.173","article-title":"Functional Cystic Fibrosis Transmembrane Conductance Regulator Expression in Cystic Fibrosis Airway Epithelial Cells by AAV6.2-Mediated Segmental Trans-Splicing","volume":"20","author":"Song","year":"2009","journal-title":"Hum. Gene Ther."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"3865","DOI":"10.1073\/pnas.0813365106","article-title":"Directed Evolution of Adeno-Associated Virus to an Infectious Respiratory Virus","volume":"106","author":"Excoffon","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2067","DOI":"10.1038\/mt.2009.155","article-title":"Generation of Novel AAV Variants by Directed Evolution for Improved CFTR Delivery to Human Ciliated Airway Epithelium","volume":"17","author":"Li","year":"2009","journal-title":"Mol. Ther."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/s41576-021-00439-4","article-title":"Drug Delivery Systems for RNA Therapeutics","volume":"23","author":"Paunovska","year":"2022","journal-title":"Nat. Rev. Genet."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1038\/gt.2008.71","article-title":"AAV-Mediated Gene Transfer for the Treatment of Hemophilia B: Problems and Prospects","volume":"15","author":"Hasbrouck","year":"2008","journal-title":"Gene Ther."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1089\/10430349950018364","article-title":"Adenoviral Gene Therapy Leads to Rapid Induction of Multiple Chemokines and Acute Neutrophil-Dependent Hepatic Injury In Vivo","volume":"10","author":"Muruve","year":"1999","journal-title":"Hum. Gene Ther."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"e17230","DOI":"10.15252\/emmm.202217230","article-title":"AAV Induces Hepatic Necroptosis and Carcinoma in Diabetic and Obese Mice Dependent on Pebp1 Pathway","volume":"15","author":"Cheng","year":"2023","journal-title":"EMBO Mol. Med."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1038\/nrd.2018.158","article-title":"Gene Therapy for Neurological Disorders: Progress and Prospects","volume":"17","author":"Deverman","year":"2018","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"16034","DOI":"10.1038\/mtm.2016.34","article-title":"Clinical Development of Gene Therapy: Results and Lessons from Recent Successes","volume":"3","author":"Kumar","year":"2016","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1915","DOI":"10.1016\/j.xphs.2020.11.035","article-title":"Development of Gene Therapy Vectors: Remaining Challenges","volume":"110","author":"Gupta","year":"2021","journal-title":"J. Pharm. Sci."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1038\/nrg1066","article-title":"Progress and Problems with the Use of Viral Vectors for Gene Therapy","volume":"4","author":"Thomas","year":"2003","journal-title":"Nat. Rev. Genet."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/j.ymthe.2020.01.001","article-title":"Immune Responses to Viral Gene Therapy Vectors","volume":"28","author":"Shirley","year":"2020","journal-title":"Mol. Ther."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1080\/14712598.2022.2060737","article-title":"Addressing High Dose AAV Toxicity\u2014\u201cOne and Done\u201d or \u201cSlower and Lower\u201d?","volume":"22","author":"Kishimoto","year":"2022","journal-title":"Expert. Opin. Biol. Ther."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1038\/43977","article-title":"Virus Treatment Questioned after Gene Therapy Death","volume":"401","author":"Lehrman","year":"1999","journal-title":"Nature"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1016\/j.ymthe.2020.01.006","article-title":"Adenovirus-Antibody Complexes Contributed to Lethal Systemic Inflammation in a Gene Therapy Trial","volume":"28","author":"Somanathan","year":"2020","journal-title":"Mol. Ther."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1089\/hum.2020.182","article-title":"Moving Forward After Two Deaths in a Gene Therapy Trial of Myotubular Myopathy","volume":"31","author":"Wilson","year":"2020","journal-title":"Hum. Gene Ther."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.omtm.2022.02.011","article-title":"Testing Preexisting Antibodies Prior to AAV Gene Transfer Therapy: Rationale, Lessons and Future Considerations","volume":"25","author":"Mendell","year":"2022","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Rabinowitz, J., Chan, Y.K., and Samulski, R.J. (2019). Adeno-Associated Virus (AAV) versus Immune Response. Viruses, 11.","DOI":"10.3390\/v11020102"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1080\/14760584.2019.1588113","article-title":"A Review of 65 Years of Human Adenovirus Seroprevalence","volume":"18","author":"Mennechet","year":"2019","journal-title":"Expert. Rev. Vaccines"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1089\/hum.2021.243","article-title":"Higher Seroprevalence of Anti-Adeno-Associated Viral Vector Neutralizing Antibodies Among Racial Minorities in the United States","volume":"33","author":"Khatri","year":"2022","journal-title":"Hum. Gene Ther."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1136\/jmg.2009.066969","article-title":"Differences in SMN1 Allele Frequencies among Ethnic Groups within North America","volume":"46","author":"Hendrickson","year":"2009","journal-title":"J. Med. Genet."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1741","DOI":"10.1016\/j.ymthe.2020.07.015","article-title":"Neutralizing the Neutralizers in AAV Gene Therapy","volume":"28","author":"Herzog","year":"2020","journal-title":"Mol. Ther."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1038\/s41591-020-0911-7","article-title":"IgG-Cleaving Endopeptidase Enables In Vivo Gene Therapy in the Presence of Anti-AAV Neutralizing Antibodies","volume":"26","author":"Leborgne","year":"2020","journal-title":"Nat. Med."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"15","DOI":"10.2217\/cer-2017-0068","article-title":"Gene Therapy: Evidence, Value and Affordability in the US Health Care System","volume":"7","author":"Hampson","year":"2018","journal-title":"J. Comp. Eff. Res."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1016\/j.jhep.2020.11.001","article-title":"Hepatotoxicity Following Administration of Onasemnogene Abeparvovec (AVXS-101) for the Treatment of Spinal Muscular Atrophy","volume":"74","author":"Chand","year":"2021","journal-title":"J. Hepatol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"675","DOI":"10.3233\/JND-221540","article-title":"Gene Therapy for Neuromuscular Diseases: Health Economic Challenges and Future Perspectives","volume":"9","author":"Landfeldt","year":"2022","journal-title":"J. Neuromuscul. Dis."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1889841","DOI":"10.1080\/20016689.2021.1889841","article-title":"An Updated Cost-Utility Model for Onasemnogene Abeparvovec (Zolgensma\u00ae) in Spinal Muscular Atrophy Type 1 Patients and Comparison with Evaluation by the Institute for Clinical and Effectiveness Review (ICER)","volume":"9","author":"Dean","year":"2021","journal-title":"J. Mark. Access Health Policy"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1016\/j.jval.2020.09.021","article-title":"Early Cost-Effectiveness of Onasemnogene Abeparvovec-Xioi (Zolgensma) and Nusinersen (Spinraza) Treatment for Spinal Muscular Atrophy I in The Netherlands With Relapse Scenarios","volume":"24","author":"Broekhoff","year":"2021","journal-title":"Value Health"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1136\/archdischild-2020-320908","article-title":"Gene Therapy for Neuromuscular Disorders: Prospects and Ethics","volume":"107","author":"Ryan","year":"2022","journal-title":"Arch. Dis. Child."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"2717","DOI":"10.1016\/j.ymthe.2018.10.017","article-title":"Addressing the Value of Gene Therapy and Enhancing Patient Access to Transformative Treatments","volume":"26","author":"Salzman","year":"2018","journal-title":"Mol. Ther."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1097\/COC.0000000000000251","article-title":"The Orphan Drug Act: Restoring the Mission to Rare Diseases","volume":"39","author":"Daniel","year":"2016","journal-title":"Am. J. Clin. Oncol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1111\/1467-9566.00174","article-title":"Waiting for the Cure: Mapping the Social Relations of Human Gene Therapy Research","volume":"21","author":"Stockdale","year":"1999","journal-title":"Sociol. Health Illn."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1136\/bmj.39566.632859.DB","article-title":"Gene Therapy Is in Danger of Being Overhyped, Expert Says","volume":"336","author":"Watts","year":"2008","journal-title":"BMJ"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1089\/hum.2019.197","article-title":"Public Acceptability of Gene Therapy and Gene Editing for Human Use: A Systematic Review","volume":"31","author":"Delhove","year":"2020","journal-title":"Hum. Gene Ther."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1038\/s41434-019-0110-7","article-title":"A Rare Disease Patient\/Caregiver Perspective on Fair Pricing and Access to Gene-Based Therapies","volume":"27","author":"White","year":"2019","journal-title":"Gene Ther."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1080\/01459740.2017.1329832","article-title":"\u201cMy Whole Life Is Ethics!\u201d Ordinary Ethics and Gene Therapy Clinical Trials","volume":"36","author":"Addison","year":"2017","journal-title":"Med. Anthropol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"264","DOI":"10.3928\/01477447-20210819-08","article-title":"The Hippocratic Oath: Analysis and Contemporary Meaning","volume":"44","author":"Sioutis","year":"2021","journal-title":"Orthopedics"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/978-1-4939-6990-6_3","article-title":"Personalized Medicine: Ethical Aspects","volume":"1606","author":"Sharrer","year":"2017","journal-title":"Methods Mol. Biol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1842","DOI":"10.1038\/mt.2009.223","article-title":"Accepting Risk in Clinical Research: Is the Gene Therapy Field Becoming Too Risk-Averse?","volume":"17","author":"Deakin","year":"2009","journal-title":"Mol. Ther."},{"key":"ref_128","unstructured":"(2023, December 10). FAERS Reporting by Patient Outcomes by Year, Available online: https:\/\/www.fda.gov\/drugs\/questions-and-answers-fdas-adverse-event-reporting-system-faers\/faers-reporting-patient-outcomes-year."},{"key":"ref_129","unstructured":"(2023, December 10). The New York Times. Available online: https:\/\/www.nytimes.com\/topic\/person\/jesse-gelsinger."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1089\/hum.2007.1214","article-title":"Protections for Participants in Gene Therapy Trials: A Patient\u2019s Perspective","volume":"19","author":"Pattee","year":"2008","journal-title":"Hum. Gene Ther."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1146\/annurev.publhealth.27.021405.102103","article-title":"Health Disparities and Health Equity: Concepts and Measurement","volume":"27","author":"Braveman","year":"2006","journal-title":"Annu. Rev. Public. Health"}],"container-title":["BioTech"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2673-6284\/13\/1\/1\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:38:36Z","timestamp":1760103516000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2673-6284\/13\/1\/1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,3]]},"references-count":131,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,3]]}},"alternative-id":["biotech13010001"],"URL":"https:\/\/doi.org\/10.3390\/biotech13010001","relation":{},"ISSN":["2673-6284"],"issn-type":[{"value":"2673-6284","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,3]]}}}