{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:56:51Z","timestamp":1785405411725,"version":"3.56.0"},"reference-count":211,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov, First Moscow State Medical University of the Ministry of Health of the Russian Federation"},{"id":[{"id":"https:\/\/ror.org\/02yqqv993","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Rare genetic disorders of the central nervous system (CNS) remain some of the most complex and challenging diseases to treat for several reasons. Targeting the CNS, especially the brain, presents one of the greatest obstacles in gene therapy using adeno-associated virus (AAV) vectors. Although various AAVs have been identified for their ability to transduce different cells in the CNS, their effectiveness and efficiency are significantly limited by the presence of neutralising antibodies (NAbs) and restricted cargo capacity. Despite these challenges, our understanding of AAV structure and technological advances continue to enable researchers to develop innovative strategies that have resulted in groundbreaking, FDA-approved therapeutic products now available for Leber congenital amaurosis (LCA) (Luxturna\u00ae), spinal muscular atrophy (SMA) (Zolgensma\u00ae), and the two recent gene therapy products for aromatic L-amino acid decarboxylase (AADC) deficiency, Kebilidi\u00ae and Upstaza\u00ae, which currently hold FDA and EMA approval, respectively. This review aims to highlight recent advances in the field of AAV gene therapy for neurological disorders, identify research gaps, and suggest areas for future investigation to enable potential breakthroughs particularly in neurodegenerative, neurodevelopmental, and neuromuscular disorders. We foresee that more tissue- and cell-specific AAV vectors designed using AI-powered platforms will emerge to precisely and efficiently target specific brain regions, transforming how CNS disorders are treated.<\/jats:p>","DOI":"10.3390\/ijms27135668","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T03:09:17Z","timestamp":1782270557000},"page":"5668","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Trends in the Engineering of Adeno-Associated Virus (AAV) for Precision Gene Delivery to the Central Nervous System (CNS)"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4078-7007","authenticated-orcid":false,"given":"Sola","family":"Oloruntimehin","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Virology, E.I. Martsinovsky Institute of Medical Parasitology, Tropical and Vector-Borne Diseases, Clinical Center, I.M. Sechenov First Moscow State Medical University, Moscow 119991, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Malogolovkin","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Virology, E.I. Martsinovsky Institute of Medical Parasitology, Tropical and Vector-Borne Diseases, Clinical Center, I.M. Sechenov First Moscow State Medical University, Moscow 119991, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"The Lancet Neurology (2024). Increasing awareness of the need for brain health. Lancet Neurol., 23, 325.","DOI":"10.1016\/S1474-4422(24)00093-0"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1001\/jamaneurol.2025.4470","article-title":"US Burden of Disorders Affecting the Nervous System: From the Global Burden of Disease 2021 Study","volume":"83","author":"Ney","year":"2026","journal-title":"JAMA Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1016\/j.apsb.2020.01.015","article-title":"Gene therapy for neurodegenerative disorders: Advances, insights and prospects","volume":"10","author":"Chen","year":"2020","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1038\/s41573-021-00139-y","article-title":"Strategies for delivering therapeutics across the blood\u2013brain barrier","volume":"20","author":"Terstappen","year":"2021","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1016\/j.ymthe.2020.12.007","article-title":"Current Clinical Applications of In Vivo Gene Therapy with AAVs","volume":"29","author":"Mendell","year":"2021","journal-title":"Mol. Ther."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1056\/NEJMoa1706198","article-title":"Single-Dose Gene-Replacement Therapy for Spinal Muscular Atrophy","volume":"377","author":"Mendell","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1089\/hum.2018.015","article-title":"Severe Toxicity in Nonhuman Primates and Piglets Following High-Dose Intravenous Administration of an Adeno-Associated Virus Vector Expressing Human SMN","volume":"29","author":"Hinderer","year":"2018","journal-title":"Hum. Gene Ther."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4251","DOI":"10.1038\/s41467-021-24524-8","article-title":"Gene therapy for aromatic L-amino acid decarboxylase deficiency by MR-guided direct delivery of AAV2-AADC to midbrain dopaminergic neurons","volume":"12","author":"Pearson","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1038\/d41573-023-00192-9","article-title":"Gene therapy zeroes in on Parkinson disease brain circuits","volume":"23","author":"Kingwell","year":"2024","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1080\/14712598.2024.2386339","article-title":"Intraparenchymal delivery of adeno-associated virus vectors for the gene therapy of neurological diseases","volume":"24","author":"Kumagai","year":"2024","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"104399","DOI":"10.1016\/j.braindev.2025.104399","article-title":"Gene therapy for lysosomal storage diseases","volume":"47","author":"Kobayashi","year":"2025","journal-title":"Brain Dev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/B978-0-323-99209-1.00008-9","article-title":"Lysosomal storage diseases","volume":"Volume 204","author":"Burlina","year":"2024","journal-title":"Handbook of Clinical Neurology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2927","DOI":"10.1038\/s41591-025-03822-4","article-title":"Dual-vector rAAVrh8 gene therapy for GM2 gangliosidosis: A phase 1\/2 trial","volume":"31","author":"Eichler","year":"2025","journal-title":"Nat. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2150","DOI":"10.1016\/j.ymthe.2020.06.021","article-title":"Pronounced Therapeutic Benefit of a Single Bidirectional AAV Vector Administered Systemically in Sandhoff Mice","volume":"28","author":"Lahey","year":"2020","journal-title":"Mol. Ther."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.omtm.2019.12.001","article-title":"AAVrh10 Vector Corrects Disease Pathology in MPS IIIA Mice and Achieves Widespread Distribution of SGSH in Large Animal Brains","volume":"17","author":"Hocquemiller","year":"2020","journal-title":"Mol. Ther.\u2014Methods Clin. Dev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1038\/s41434-022-00368-9","article-title":"IgG-cleavage protein allows therapeutic AAV gene delivery in passively immunized MPS IIIA mice","volume":"30","author":"Bobo","year":"2023","journal-title":"Gene Ther."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e12464","DOI":"10.1002\/jev2.12464","article-title":"AAV gene replacement therapy for treating MPS IIIC: Facilitating bystander effects via EV-mRNA cargo","volume":"13","author":"Bobo","year":"2024","journal-title":"J. Extracell. Vesicles"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e00511","DOI":"10.1016\/j.neurot.2024.e00511","article-title":"Cross-species RNAi therapy via AAV delivery alleviates neuropathic pain by targeting GCH1","volume":"22","author":"Chang","year":"2025","journal-title":"Neurotherapeutics"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1007\/s00702-023-02673-y","article-title":"Catecholamines and Parkinson\u2019s disease: Tyrosine hydroxylase (TH) over tetrahydrobiopterin (BH4) and GTP cyclohydrolase I (GCH1) to cytokines, neuromelanin, and gene therapy: A historical overview","volume":"131","author":"Nagatsu","year":"2024","journal-title":"J. Neural Transm."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e00435","DOI":"10.1016\/j.neurot.2024.e00435","article-title":"Immune responses to central nervous system directed adeno-associated virus gene therapy: Does direct CNS delivery make a difference?","volume":"21","author":"Harkins","year":"2024","journal-title":"Neurotherapeutics"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1038\/s41392-024-01780-w","article-title":"Adeno-associated virus as a delivery vector for gene therapy of human diseases","volume":"9","author":"Wang","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_22","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_23","doi-asserted-by":"crossref","first-page":"101640","DOI":"10.1016\/j.omtm.2025.101640","article-title":"AAV-mediated gene therapy for the CNS: The case for early treatment","volume":"33","year":"2025","journal-title":"Mol. Ther.\u2014Methods Clin. Dev."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Zwi-Dantsis, L., Mohamed, S., Massaro, G., and Moeendarbary, E. (2025). Adeno-Associated Virus Vectors: Principles, Practices, and Prospects in Gene Therapy. Viruses, 17.","DOI":"10.3390\/v17020239"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Wang, S., and Xiao, L. (2025). Progress in AAV-Mediated In Vivo Gene Therapy and Its Applications in Central Nervous System Diseases. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26052213"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Issa, S.S., Shaimardanova, A.A., Solovyeva, V.V., and Rizvanov, A.A. (2023). Various AAV Serotypes and Their Applications in Gene Therapy: An Overview. Cells, 12.","DOI":"10.3390\/cells12050785"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1146\/annurev-neuro-111020-100834","article-title":"Adeno-Associated Virus Toolkit to Target Diverse Brain Cells","volume":"45","author":"Challis","year":"2022","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e1607","DOI":"10.1002\/ctm2.1607","article-title":"Optimization strategies and advances in the research and development of AAV-based gene therapy to deliver large transgenes","volume":"14","author":"Kolesnik","year":"2024","journal-title":"Clin. Transl. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1016\/j.tim.2021.09.005","article-title":"Adeno-associated virus (AAV) cell entry: Structural insights","volume":"30","author":"Meyer","year":"2022","journal-title":"Trends Microbiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.ymthe.2019.11.005","article-title":"GPR108 Is a Highly Conserved AAV Entry Factor","volume":"28","author":"Dudek","year":"2020","journal-title":"Mol. Ther."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1016\/j.omtm.2020.03.012","article-title":"Pooled Screens Identify GPR108 and TM9SF2 as Host Cell Factors Critical for AAV Transduction","volume":"17","author":"Meisen","year":"2020","journal-title":"Mol. Ther.\u2014Methods Clin. Dev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2777","DOI":"10.1128\/JVI.74.6.2777-2785.2000","article-title":"Infectious Entry Pathway of Adeno-Associated Virus and Adeno-Associated Virus Vectors","volume":"74","author":"Bartlett","year":"2000","journal-title":"J. Virol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.virol.2010.09.025","article-title":"Intrinsic phospholipase A2 activity of adeno-associated virus is involved in endosomal escape of incoming particles","volume":"409","author":"Stahnke","year":"2011","journal-title":"Virology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1038\/mt.2010.170","article-title":"Proteasome Inhibitors Enhance Gene Delivery by AAV Virus Vectors Expressing Large Genomes in Hemophilia Mouse and Dog Models: A Strategy for Broad Clinical Application","volume":"18","author":"Monahan","year":"2010","journal-title":"Mol. Ther."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1038\/s41434-021-00243-z","article-title":"Intracellular trafficking of adeno-associated virus (AAV) vectors: Challenges and future directions","volume":"28","author":"Riyad","year":"2021","journal-title":"Gene Ther."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4132","DOI":"10.1128\/JVI.02660-13","article-title":"Recombinant Adeno-Associated Virus Utilizes Host Cell Nuclear Import Machinery to Enter the Nucleus","volume":"88","author":"Nicolson","year":"2014","journal-title":"J. Virol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1038\/sj.gt.3301514","article-title":"Self-complementary recombinant adeno-associated virus (scAAV) vectors promote efficient transduction independently of DNA synthesis","volume":"8","author":"McCarty","year":"2001","journal-title":"Gene Ther."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1648","DOI":"10.1038\/mt.2008.171","article-title":"Self-complementary AAV Vectors; Advances and Applications","volume":"16","author":"McCarty","year":"2008","journal-title":"Mol. Ther."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"101494","DOI":"10.1016\/j.omtm.2025.101494","article-title":"Common AAV gene therapy vectors show nonselective transduction of ex vivo human brain tissue","volume":"33","author":"McGinnis","year":"2025","journal-title":"Mol. Ther.\u2014Methods Clin. Dev."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Sharma, S., Joshi, V., and Kumar, V. (2025). Implications of AAV Serotypes in Neurological Disorders: Current Clinical Applications and Challenges. Clin. Transl. Neurosci., 9.","DOI":"10.3390\/ctn9030032"},{"key":"ref_41","unstructured":"Estipona, D. (2026, May 06). A Review of Viral Vectors in Gene Therapy. Available online: https:\/\/www.biocompare.com\/Editorial-Articles\/619487-A-Review-of-Viral-Vectors-in-Gene-Therapy\/."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"102264","DOI":"10.1016\/j.omtn.2024.102264","article-title":"Enhanced AAV transduction across preclinical CNS models: A comparative study in human brain organoids with cross-species evaluations","volume":"35","author":"Drouyer","year":"2024","journal-title":"Mol. Ther.\u2014Nucleic Acids"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1089\/hum.2023.067","article-title":"Assessment of Safety and Biodistribution of AAVrh.10hCLN2 Following Intracisternal Administration in Nonhuman Primates for the Treatment of CLN2 Batten Disease","volume":"34","author":"De","year":"2023","journal-title":"Hum. Gene Ther."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1186\/s12967-023-04816-x","article-title":"Brain-targeted delivery of neuroprotective survival gene minimizing hematopoietic cell contamination: Implications for Parkinson\u2019s disease treatment","volume":"22","author":"Lee","year":"2024","journal-title":"J. Transl. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1089\/hum.2022.163","article-title":"Biodistribution of Adeno-Associated Virus Gene Therapy Following Cerebrospinal Fluid-Directed Administration","volume":"34","author":"Chen","year":"2023","journal-title":"Hum. Gene Ther."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3123","DOI":"10.1016\/j.ymthe.2023.10.015","article-title":"Lethal immunotoxicity in high-dose systemic AAV therapy","volume":"31","author":"Duan","year":"2023","journal-title":"Mol. Ther."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Shen, W., Liu, S., and Ou, L. (2022). rAAV immunogenicity, toxicity, and durability in 255 clinical trials: A meta-analysis. Front. Immunol., 13, Correction in Front. Immunol.\u00a02023, 13, 1104646.","DOI":"10.3389\/fimmu.2022.1001263"},{"key":"ref_48","unstructured":"FDA (2025). FDA Investigating Deaths Due to Acute Liver Failure Following Treatment with Sarepta\u2019s AAVrh74 Gene Therapies, FDA."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.omtm.2020.10.011","article-title":"CNS Transduction Benefits of AAV-PHP.eB over AAV9 Are Dependent on Administration Route and Mouse Strain","volume":"19","author":"Mathiesen","year":"2020","journal-title":"Mol. Ther.\u2014Methods Clin. Dev."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1038\/s41593-021-00969-4","article-title":"AAV capsid variants with brain-wide transgene expression and decreased liver targeting after intravenous delivery in mouse and marmoset","volume":"25","author":"Goertsen","year":"2022","journal-title":"Nat. Neurosci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"101116","DOI":"10.1016\/j.crmeth.2025.101116","article-title":"AAV vectors for specific and efficient gene expression in microglia","volume":"5","author":"Aoki","year":"2025","journal-title":"Cell Rep. Methods"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.omtm.2022.12.014","article-title":"Characterization of the humanized FRG mouse model and development of an AAV-LK03 variant with improved liver lobular biodistribution","volume":"28","author":"Navarro","year":"2023","journal-title":"Mol. Ther.\u2014Methods Clin. Dev."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Rico, A.J., Jolinon, N., Torre-Muruzabal, T., Linden, R.M., Henckaerts, E., and Lanciego, J.L. (2026). Biodistribution of AAV-TT and AAV9 in the Nonhuman Primate Brain. Hum. Gene Ther., 10430342261427733.","DOI":"10.1177\/10430342261427733"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1126\/science.adm8386","article-title":"An AAV capsid reprogrammed to bind human transferrin receptor mediates brain-wide gene delivery","volume":"384","author":"Huang","year":"2024","journal-title":"Science"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1172","DOI":"10.1038\/nn.4593","article-title":"Engineered AAVs for efficient noninvasive gene delivery to the central and peripheral nervous systems","volume":"20","author":"Chan","year":"2017","journal-title":"Nat. Neurosci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1038\/nbt.3440","article-title":"Cre-dependent selection yields AAV variants for widespread gene transfer to the adult brain","volume":"34","author":"Deverman","year":"2016","journal-title":"Nat. Biotechnol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1016\/j.ymthe.2018.01.018","article-title":"The Neurotropic Properties of AAV-PHP.B Are Limited to C57BL\/6J Mice","volume":"26","author":"Hordeaux","year":"2018","journal-title":"Mol. Ther."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/j.omtm.2019.10.007","article-title":"Selection of an Efficient AAV Vector for Robust CNS Transgene Expression","volume":"15","author":"Hanlon","year":"2019","journal-title":"Mol. Ther.\u2014Methods Clin. Dev."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1038\/s41576-019-0205-4","article-title":"Engineering adeno-associated virus vectors for gene therapy","volume":"21","author":"Li","year":"2020","journal-title":"Nat. Rev. Genet."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/j.omtn.2018.03.007","article-title":"CRISPR\/Cas9 Mediated Disruption of the Swedish APP Allele as a Therapeutic Approach for Early-Onset Alzheimer\u2019s Disease","volume":"11","author":"Zaborowski","year":"2018","journal-title":"Mol. Ther.\u2014Nucleic Acids"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/s41434-020-0169-1","article-title":"Optimization of adeno-associated viral vector-mediated transduction of the corticospinal tract: Comparison of four promoters","volume":"28","author":"Nieuwenhuis","year":"2021","journal-title":"Gene Ther."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1089\/hum.2010.245","article-title":"Optimizing Promoters for Recombinant Adeno-Associated Virus-Mediated Gene Expression in the Peripheral and Central Nervous System Using Self-Complementary Vectors","volume":"22","author":"Gray","year":"2011","journal-title":"Hum. Gene Ther."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Qin, J.Y., Zhang, L., Clift, K.L., Hulur, I., Xiang, A.P., Ren, B.-Z., and Lahn, B.T. (2010). Systematic Comparison of Constitutive Promoters and the Doxycycline-Inducible Promoter. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0010611"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.omtm.2019.06.006","article-title":"Neuronal Activation Stimulates Cytomegalovirus Promoter-Driven Transgene Expression","volume":"14","author":"Dossat","year":"2019","journal-title":"Mol. Ther.\u2014Methods Clin. Dev."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1089\/hum.2020.196","article-title":"Adeno-Associated Virus Capsid-Promoter Interactions in the Brain Translate from Rat to the Nonhuman Primate","volume":"31","author":"Bohlen","year":"2020","journal-title":"Hum. Gene Ther."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Hollidge, B.S., Carroll, H.B., Qian, R., Fuller, M.L., Giles, A.R., Mercer, A.C., Danos, O., Liu, Y., Bruder, J.T., and Smith, J.B. (2022). Kinetics and durability of transgene expression after intrastriatal injection of AAV9 vectors. Front. Neurol., 13.","DOI":"10.3389\/fneur.2022.1051559"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"135956","DOI":"10.1016\/j.neulet.2021.135956","article-title":"Comparative study of neuron-specific promoters in mouse brain transduced by intravenously administered AAV-PHP.eB","volume":"756","author":"Radhiyanti","year":"2021","journal-title":"Neurosci. Lett."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Chesnokova, E., Bal, N., Alhalabi, G., and Balaban, P. (2025). Regulatory Elements for Gene Therapy of Epilepsy. Cells, 14.","DOI":"10.3390\/cells14030236"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"107999","DOI":"10.1016\/j.heares.2020.107999","article-title":"Characterization of promoters for adeno-associated virus mediated efficient Cas9 activation in adult Cas9 knock-in murine cochleae","volume":"394","author":"Zhao","year":"2020","journal-title":"Hear. Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1021\/acssynbio.5b00266","article-title":"Quantitative Analyses of Core Promoters Enable Precise Engineering of Regulated Gene Expression in Mammalian Cells","volume":"5","author":"Ede","year":"2016","journal-title":"ACS Synth. Biol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1016\/j.omtm.2023.05.013","article-title":"Strong ubiquitous micro-promoters for recombinant adeno-associated viral vectors","volume":"29","author":"Chai","year":"2023","journal-title":"Mol. Ther.\u2014Methods Clin. Dev."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Yang, R., Li, Y., Zhao, X., Wang, L., Wu, J., and Sima, J. (2025). AAV-based temporal APOE4-to-APOE2 replacement reveals rebound adaptation and RAB24-mediated A\u03b2 and cholesterol dysregulation. bioRxiv.","DOI":"10.1101\/2025.07.08.663694"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"101649","DOI":"10.1016\/j.gendis.2025.101649","article-title":"Hippocampus-targeted BDNF gene therapy to rescue cognitive impairments of Alzheimer\u2019s disease in multiple mouse models","volume":"13","author":"Tang","year":"2026","journal-title":"Genes Dis."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.omtm.2022.09.012","article-title":"Hypothalamic AAV-BDNF gene therapy improves metabolic function and behavior in the Magel2-null mouse model of Prader-Willi syndrome","volume":"27","author":"Queen","year":"2022","journal-title":"Mol. Ther.\u2014Methods Clin. Dev."},{"key":"ref_75","unstructured":"Sivasankaran, R. (2025, January 13\u201317). Intravenous delivery of VY1706, a CNS penetrant AAV gene therapy for Alzheimer\u2019s disease, provides broad Tau lowering in NHP. Proceedings of the ASGCT 2025, New Orleans, LA, USA."},{"key":"ref_76","unstructured":"Retzlaff, C., Wimalasena, N., Calitri, R., Rappoli, D., Tsolias, A., Ren, X., Shah, I., O\u2019Brien, J., Chen, J., and Nonnenmacher, M. (2025, January 13\u201317). One-time Delivery of a Vectorized Anti-amyloid Antibody for Increased and Sustained CNS Expression and Target Engagement. Proceedings of the ASGCT 2025, New Orleans, LA, USA."},{"key":"ref_77","unstructured":"PHARMABIZ (2025, August 22). Klotho Neurosciences Begins Manufacturing of KLTO-202 Product Candidate Using AAVnerGene\u2019s Platform Technology. Available online: https:\/\/www.pharmabiz.com\/NewsDetails.aspx?aid=180674&sid=2."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"5838","DOI":"10.1093\/hmg\/ddu277","article-title":"Coding variants in TREM2 increase risk for Alzheimer\u2019s disease","volume":"23","author":"Jin","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1016\/j.immuni.2025.04.022","article-title":"Microglial and TREM2 dialogues in the developing brain","volume":"58","author":"Morini","year":"2025","journal-title":"Immunity"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1056\/NEJMoa1211103","article-title":"Variant of TREM2 Associated with the Risk of Alzheimer\u2019s Disease","volume":"368","author":"Jonsson","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"e20200785","DOI":"10.1084\/jem.20200785","article-title":"Anti-human TREM2 induces microglia proliferation and reduces pathology in an Alzheimer\u2019s disease model","volume":"217","author":"Wang","year":"2020","journal-title":"J. Exp. Med."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1084\/jem.20030027","article-title":"DAP12\/TREM2 Deficiency Results in Impaired Osteoclast Differentiation and Osteoporotic Features","volume":"198","author":"Paloneva","year":"2003","journal-title":"J. Exp. Med."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Ma, Y., Hu, X., Karako, K., Song, P., Tang, W., and Xia, Y. (2025). The potential and challenges of TREM2-targeted therapy in Alzheimer\u2019s disease: Insights from the INVOKE-2 study. Front. Aging Neurosci., 17.","DOI":"10.3389\/fnagi.2025.1576020"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"83","DOI":"10.3233\/JAD-215699","article-title":"Alzheimer\u2019s Disease: Key Insights from Two Decades of Clinical Trial Failures","volume":"87","author":"Kim","year":"2022","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.1002\/jmri.29804","article-title":"MR-Guidance of Gene Therapy for Brain Diseases: Moving from Palliative Treatment to Cures","volume":"62","author":"Bermudez","year":"2025","journal-title":"J. Magn. Reson. Imaging"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"14016","DOI":"10.1038\/mtm.2014.16","article-title":"Quantitative, noninvasive, in vivo longitudinal monitoring of gene expression in the brain by co-AAV transduction with a PET reporter gene","volume":"1","author":"Yoon","year":"2014","journal-title":"Mol. Ther.\u2014Methods Clin. Dev."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1053\/snuc.2001.26209","article-title":"Monitoring gene therapy with reporter gene imaging","volume":"31","author":"Ray","year":"2001","journal-title":"Semin. Nucl. Med."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1038\/sj.gt.3300877","article-title":"Repetitive, non-invasive imaging of the dopamine D2 receptor as a reporter gene in living animals","volume":"6","author":"MacLaren","year":"1999","journal-title":"Gene Ther."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1490","DOI":"10.1038\/sj.gt.3301542","article-title":"Noninvasive, quantitative imaging in living animals of a mutant dopamine D2 receptor reporter gene in which ligand binding is uncoupled from signal transduction","volume":"8","author":"Liang","year":"2001","journal-title":"Gene Ther."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.2967\/jnumed.110.084426","article-title":"A PET brain reporter gene system based on type 2 cannabinoid receptors","volume":"52","author":"Vandeputte","year":"2011","journal-title":"J. Nucl. Med."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1016\/j.ymthe.2003.12.001","article-title":"Quantitative imaging of Na\/I symporter transgene expression using positron emission tomography in the living animal","volume":"9","author":"Aboagye","year":"2004","journal-title":"Mol. Ther."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"2785","DOI":"10.1073\/pnas.97.6.2785","article-title":"A mutant herpes simplex virus type 1 thymidine kinase reporter gene shows improved sensitivity for imaging reporter gene expression with positron emission tomography","volume":"97","author":"Gambhir","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_93","first-page":"4333","article-title":"Imaging herpes virus thymidine kinase gene transfer and expression by positron emission tomography","volume":"58","author":"Tjuvajev","year":"1998","journal-title":"Cancer Res."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"4257","DOI":"10.1038\/s41598-025-86815-0","article-title":"PET imaging of AAV9 and AAVBR1 trafficking in normal mice","volume":"15","author":"Bansal","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"92","DOI":"10.5214\/ans.0972-7531.1017209","article-title":"The current status of gene therapy for Parkinson\u2019s disease","volume":"17","author":"Muramatsu","year":"2010","journal-title":"Ann. Neurosci."},{"key":"ref_96","unstructured":"Meglio, M. (2025). Gene Therapy AAV-GAD Gains Regenerative Medicine Advanced Therapy Designation as Potential Parkinson Treatment. NeurologyLive."},{"key":"ref_97","unstructured":"Taylor, P. (2024). MeiraGTx Plans to Take Parkinson\u2019s Gene Therapy into Phase 3. Precis. Med. Online."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"5394","DOI":"10.1016\/j.cell.2023.10.004","article-title":"Circuit-specific gene therapy reverses core symptoms in a primate Parkinson\u2019s disease model","volume":"186","author":"Chen","year":"2023","journal-title":"Cell"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1651","DOI":"10.1056\/NEJMoa0901281","article-title":"Multicenter Analysis of Glucocerebrosidase Mutations in Parkinson\u2019s Disease","volume":"361","author":"Sidransky","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1038\/s41531-025-01063-3","article-title":"Severe GBA1 variants drive the GBA1-PD clinical phenotype: Implications for counselling and clinical trials","volume":"11","author":"Menozzi","year":"2025","journal-title":"npj Park. Dis."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"2727","DOI":"10.1016\/j.ymthe.2017.08.004","article-title":"AAV-PHP.B-Mediated Global-Scale Expression in the Mouse Nervous System Enables GBA1 Gene Therapy for Wide Protection from Synucleinopathy","volume":"25","author":"Morabito","year":"2017","journal-title":"Mol. Ther."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/j.nbd.2015.09.009","article-title":"Glucocerebrosidase gene therapy prevents \u03b1-synucleinopathy of midbrain dopamine neurons","volume":"82","author":"Rocha","year":"2015","journal-title":"Neurobiol. Dis."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"3359","DOI":"10.1007\/s10072-025-08294-5","article-title":"ALS global day 2025: Research and clinical advances","volume":"46","author":"Ticozzi","year":"2025","journal-title":"Neurol. Sci."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s40035-025-00477-6","article-title":"Gene therapy breakthroughs in ALS: A beacon of hope for 20% of ALS patients","volume":"14","author":"Xie","year":"2025","journal-title":"Transl. Neurodegener."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/S1474-4422(25)00026-2","article-title":"Amyotrophic lateral sclerosis caused by hexanucleotide repeat expansions in C9orf72: From genetics to therapeutics","volume":"24","author":"Mizielinska","year":"2025","journal-title":"Lancet Neurol."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Suthar, S.K., and Lee, S.-Y. (2023). The Role of Superoxide Dismutase 1 in Amyotrophic Lateral Sclerosis: Identification of Signaling Pathways, Regulators, Molecular Interaction Networks, and Biological Functions through Bioinformatics. Brain Sci., 13.","DOI":"10.3390\/brainsci13010151"},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Peggion, C., Scalcon, V., Massimino, M.L., Nies, K., Lopreiato, R., Rigobello, M.P., and Bertoli, A. (2022). SOD1 in ALS: Taking Stock in Pathogenic Mechanisms and the Role of Glial and Muscle Cells. Antioxidants, 11.","DOI":"10.3390\/antiox11040614"},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Alzheimer\u2019s Disease Neuroimaging Initiative, Iacoangeli, A., Al Khleifat, A., Jones, A.R., Sproviero, W., Shatunov, A., Opie-Martin, S., Morrison, K.E., Shaw, P.J., and Shaw, C.E. (2019). C9orf72 intermediate expansions of 24\u201330 repeats are associated with ALS. Acta Neuropathol. Commun., 7, 115.","DOI":"10.1186\/s40478-019-0724-4"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"2217","DOI":"10.1038\/s41593-025-02075-1","article-title":"C9orf72 hexanucleotide repeat expansions impair microglial response in ALS","volume":"28","author":"Masrori","year":"2025","journal-title":"Nat. Neurosci."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"5334","DOI":"10.1038\/s41467-025-60497-8","article-title":"AAV-based delivery of RNAi targeting ataxin-2 improves survival and pathology in TDP-43 mice","volume":"16","author":"Amado","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"4745","DOI":"10.1038\/s44318-025-00506-0","article-title":"ALS-associated RNA-binding proteins promote UNC13A transcription through REST downregulation","volume":"44","author":"Watanabe","year":"2025","journal-title":"EMBO J."},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Zhang, X., He, J., Song, N., Li, X., Wang, W., Hu, Y., Li, Q., Hu, Y., Yin, C., and Zhao, P. (2025). Cell-autonomous and non-cell-autonomous effect of TRIM72 on ALS disease progression. bioRxiv.","DOI":"10.1101\/2025.01.09.632080"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"13363","DOI":"10.1073\/pnas.95.23.13363","article-title":"Prions","volume":"95","author":"Prusiner","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"10615","DOI":"10.1093\/nar\/gkaa616","article-title":"Prion protein lowering is a disease-modifying therapy across prion disease stages, strains and endpoints","volume":"48","author":"Minikel","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.sbi.2008.12.007","article-title":"Prion protein misfolding and disease","volume":"19","author":"Moore","year":"2009","journal-title":"Curr. Opin. Struct. Biol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"e2019631118","DOI":"10.1073\/pnas.2019631118","article-title":"Mechanism of misfolding of the human prion protein revealed by a pathological mutation","volume":"118","author":"Barritt","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1038\/s41591-025-03540-x","article-title":"Author Correction: In vivo base editing extends lifespan of a humanized mouse model of prion disease","volume":"31","author":"An","year":"2025","journal-title":"Nat. Med."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"ado7082","DOI":"10.1126\/science.ado7082","article-title":"Brainwide silencing of prion protein by AAV-mediated delivery of an engineered compact epigenetic editor","volume":"384","author":"Neumann","year":"2024","journal-title":"Science"},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Chou, S.-W., Mortberg, M.A., Marlen, K., Ojala, D.S., Parman, T., Howard, M., DeSouza-Lenz, K., Lian, Y., Mehrabian, M., and Tiffany, M. (2025). Zinc Finger Repressors mediate widespread PRNP lowering in the nonhuman primate brain and profoundly extend survival in prion disease mice. bioRxiv.","DOI":"10.1101\/2025.03.05.636713"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1080\/17460751.2024.2353496","article-title":"Industry updates from the field of stem cell research and regenerative medicine in March 2024","volume":"19","author":"Ilic","year":"2024","journal-title":"Regen. Med."},{"key":"ref_121","unstructured":"Food and Drug Administration (FDA) (2024). FDA Approves First Gene Therapy for Treatment of Aromatic L-amino Acid Decarboxylase Deficiency, Food and Drug Administration (FDA)."},{"key":"ref_122","unstructured":"Texas Children\u2019s Hospital (2025). Texas Children\u2019s Provides New Breakthrough Treatment for Patient with Rare Neurological Disorder, Texas Children\u2019s Hospital."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1038\/s41572-022-00380-8","article-title":"Spinal muscular atrophy","volume":"8","author":"Mercuri","year":"2022","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"2479","DOI":"10.1016\/j.ymthe.2025.04.045","article-title":"Current clinical applications of AAV-mediated gene therapy","volume":"33","author":"Byrne","year":"2025","journal-title":"Mol. Ther."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"889","DOI":"10.3233\/JND-230248","article-title":"A Systematic Literature Review of the Natural History of Respiratory, Swallowing, Feeding, and Speech Functions in Spinal Muscular Atrophy (SMA)","volume":"11","author":"Batson","year":"2024","journal-title":"J. Neuromuscul. Dis."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1111\/joa.12083","article-title":"Spinal muscular atrophy: A motor neuron disorder or a multi-organ disease?","volume":"224","author":"Shababi","year":"2014","journal-title":"J. Anat."},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Angilletta, I., Ferrante, R., Giansante, R., Lombardi, L., Babore, A., Dell\u2019Elice, A., Alessandrelli, E., Notarangelo, S., Ranaudo, M., and Palmarini, C. (2023). Spinal Muscular Atrophy: An Evolving Scenario through New Perspectives in Diagnosis and Advances in Therapies. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241914873"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1564","DOI":"10.1212\/CON.0000000000001338","article-title":"Spinal Muscular Atrophy","volume":"29","author":"Oskoui","year":"2023","journal-title":"Continuum"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"100346","DOI":"10.1016\/j.xcrm.2021.100346","article-title":"Spinal muscular atrophy: From approved therapies to future therapeutic targets for personalized medicine","volume":"2","author":"Chaytow","year":"2021","journal-title":"Cell Rep. Med."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1007\/s40263-022-00941-1","article-title":"Onasemnogene Abeparvovec: A Review in Spinal Muscular Atrophy","volume":"36","author":"Blair","year":"2022","journal-title":"CNS Drugs"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"101550","DOI":"10.1016\/j.omtm.2025.101550","article-title":"Safety through design: Expanding options for spinal muscular atrophy gene therapy","volume":"33","author":"Groen","year":"2025","journal-title":"Mol. Ther.\u2014Methods Clin. Dev."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"101475","DOI":"10.1016\/j.omtm.2025.101475","article-title":"Efficacy and preliminary safety assessment of EXG001-307 AAV gene therapy for spinal muscular atrophy","volume":"33","author":"Song","year":"2025","journal-title":"Mol. Ther.\u2014Methods Clin. Dev."},{"key":"ref_133","unstructured":"Stansfield, N. (2025). Spinal Muscular Atrophy Month 2025: Looking Back at News and Expert Insights, CGTLive."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/s12929-025-01123-z","article-title":"Treating neuromuscular diseases: Unveiling gene therapy breakthroughs and pioneering future applications","volume":"32","author":"Wu","year":"2025","journal-title":"J. Biomed. Sci."},{"key":"ref_135","first-page":"1025","article-title":"Interim results for RGX-381: A first in human phase 1\/2 clinical trial of AAV.CB7.hCLN2 gene therapy for CLN2 Batten disease-associated retinopathy","volume":"65","author":"Henderson","year":"2024","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1089\/hum.2024.182","article-title":"Twenty-Year Survival Analysis of Adeno-Associated Virus Vector Serotype 2-Mediated Gene Therapy to the Central Nervous System for CLN2 Disease","volume":"36","author":"Sondhi","year":"2025","journal-title":"Hum. Gene Ther."},{"key":"ref_137","unstructured":"de los Reyes, E., Aylward, S., Islam, M., Meyer, K., Stefanelli, E., Jiang, H., Weimer, J., and Goldman, M. (2021, January 8\u201312). An Open-Label, Phase 1\/2a, AAV9-CLN3 Gene Transfer Clinical Trial for Juvenile Neuronal Ceroid Lipofuscinosis. Proceedings of the WORLDSymposium 2021, Virtual Meeting."},{"key":"ref_138","unstructured":"Gujjarlapudi, S. (2026, May 05). AAV Gene Therapy Shows Positive Results in Batten Disease Trial. Available online: https:\/\/www.clinicaltrialsarena.com\/news\/aav-gene-therapy-shows-positive-results-in-batten-disease-trial\/?cf-view&cf-closed."},{"key":"ref_139","unstructured":"Payesko, J. (2019). Gene Therapy for CLN6 Batten Disease Shows Positive Interim Results. NeurologyLive."},{"key":"ref_140","doi-asserted-by":"crossref","unstructured":"Wood, S.R., and Bigger, B.W. (2022). Delivering gene therapy for mucopolysaccharide diseases. Front. Mol. Biosci., 9.","DOI":"10.3389\/fmolb.2022.965089"},{"key":"ref_141","first-page":"EVIDoa2200052","article-title":"Liver-Directed Adeno-Associated Virus\u2013Mediated Gene Therapy for Mucopolysaccharidosis Type VI","volume":"1","author":"Ferla","year":"2022","journal-title":"NEJM Evid."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"100544","DOI":"10.1016\/j.medj.2024.10.021","article-title":"Multi-year enzyme expression in patients with mucopolysaccharidosis type VI after liver-directed gene therapy","volume":"6","author":"Rossi","year":"2025","journal-title":"Med"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"101369","DOI":"10.1016\/j.omtm.2024.101369","article-title":"Intrathecal or intravenous AAV9-IDUA\/RGX-111 at minimal effective dose prevents cardiac, skeletal and neurologic manifestations of murine MPS I","volume":"32","author":"Belur","year":"2024","journal-title":"Mol. Ther.\u2014Methods Clin. Dev."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"S76","DOI":"10.1016\/j.ymgme.2020.12.177","article-title":"RGX-121 gene therapy for severe mucopolysaccharidosis type II (MPS II): Interim results of an ongoing first in human trial","volume":"132","author":"Nevoret","year":"2021","journal-title":"Mol. Genet. Metab."},{"key":"ref_145","doi-asserted-by":"crossref","unstructured":"Zapolnik, P., and Pyrkosz, A. (2021). Gene Therapy for Mucopolysaccharidosis Type II\u2014A Review of the Current Possibilities. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22115490"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"e195268","DOI":"10.1172\/JCI195268","article-title":"Reduced heparan sulfate levels in cerebrospinal fluid reflect brain neuron correction in Sanfilippo B mice","volume":"135","author":"Le","year":"2025","journal-title":"J. Clin. Investig."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1007\/s10545-018-0221-0","article-title":"The efficacy of intracerebroventricular idursulfase-beta enzyme replacement therapy in mucopolysaccharidosis II murine model: Heparan sulfate in cerebrospinal fluid as a clinical biomarker of neuropathology","volume":"41","author":"Sohn","year":"2018","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"4415","DOI":"10.1212\/WNL.0000000000211655","article-title":"Treatment with UX111 Gene Therapy Rapidly Reduced Heparan Sulfate (HS) Exposure in Cerebrospinal Fluid (CSF) and Improved Long-term Cognitive Function in Children with Mucopolysaccharidosis IIIA (MPS IIIA) (S31.001)","volume":"104","author":"Lau","year":"2025","journal-title":"Neurology"},{"key":"ref_149","unstructured":"U.S Food & Drug Administration (2025). Complete Response Letter For UX111, U.S Food & Drug Administration."},{"key":"ref_150","doi-asserted-by":"crossref","unstructured":"Maguire, A.S., and Martin, D.R. (2021). White Matter Pathology as a Barrier to Gangliosidosis Gene Therapy. Front. Cell. Neurosci., 15.","DOI":"10.3389\/fncel.2021.682106"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"4353","DOI":"10.1093\/hmg\/ddv168","article-title":"Systemic AAV9 gene transfer in adult GM1 gangliosidosis mice reduces lysosomal storage in CNS and extends lifespan","volume":"24","author":"Weismann","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"ref_152","unstructured":"Hoffman, M. (2025). Dual-Vector AAV Gene Therapy for GM2 Gangliosidosis Shows Promising Early Outcomes, CGTLive."},{"key":"ref_153","doi-asserted-by":"crossref","unstructured":"Lewis, C.J., D\u2019Souza, P., Johnston, J.M., Acosta, M.T., Farmer, C., Baker, E.H., Crowell, A., Mojica, Y., Rahman, S., and Joseph, L. (2025). AAV9 Gene Therapy in GM1 Gangliosidosis Type II: A Phase 1\/2 Trial. medRxiv.","DOI":"10.1101\/2025.07.28.25332074"},{"key":"ref_154","doi-asserted-by":"crossref","unstructured":"Flotte, T.R., Blackwood, M., Arjomandnejad, M., Harkins, A., Sylvia, K., Iyer, S., Kokoski, D., Artinian, R., and Keeler, A.M. (2025). Characterization of Immune Responses to rAAVrh8 Gene Therapy for GM2 Gangliosidosis in Phase 1\/2 Trial. medRxiv.","DOI":"10.1101\/2025.05.07.25327170"},{"key":"ref_155","doi-asserted-by":"crossref","unstructured":"Nygaard, G., Szigetvari, P.D., Grindheim, A.K., Ruoff, P., Martinez, A., Haavik, J., Kleppe, R., and Flydal, M.I. (2021). Personalized Medicine to Improve Treatment of Dopa-Responsive Dystonia-A Focus on Tyrosine Hydroxylase Deficiency. J. Pers. Med., 11.","DOI":"10.3390\/jpm11111186"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"44","DOI":"10.4103\/ijmbs.ijmbs_23_21","article-title":"Dopa-responsive dystonia: Guanosine triphosphate cyclohydrolase 1, tyrosine hydroxylase, and sepiapterin reductase","volume":"13","author":"Pitton","year":"2021","journal-title":"Ibnosina J. Med. Biomed. Sci."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1002\/mds.28874","article-title":"Relationship of Genotype, Phenotype, and Treatment in Dopa-Responsive Dystonia: MDSGene Review","volume":"37","author":"Weissbach","year":"2022","journal-title":"Mov. Disord."},{"key":"ref_158","first-page":"FV15_04","article-title":"Dopamine-responsive dystonia: Clinical and therapeutic variability with identical genetic defect","volume":"44","author":"Zaugg","year":"2013","journal-title":"Neuropediatrics"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1186\/s13023-025-03893-z","article-title":"In vivo applications and toxicities of AAV-based gene therapies in rare diseases","volume":"20","author":"Zhao","year":"2025","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1007\/s00415-025-12940-5","article-title":"Genetic therapies for movement disorders-current status","volume":"272","author":"Sartorelli","year":"2025","journal-title":"J. Neurol."},{"key":"ref_161","doi-asserted-by":"crossref","unstructured":"Ng, J., Barral, S., Waddington, S.N., and Kurian, M.A. (2023). Dopamine Transporter Deficiency Syndrome (DTDS): Expanding the Clinical Phenotype and Precision Medicine Approaches. Cells, 12.","DOI":"10.3390\/cells12131737"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1007\/s40263-025-01203-6","article-title":"Investigational Gene Therapies for Parkinson\u2019s Disease","volume":"39","author":"Phielipp","year":"2025","journal-title":"CNS Drugs"},{"key":"ref_163","doi-asserted-by":"crossref","unstructured":"Huang, Q., Chen, A.T., Chan, K.Y., Sorensen, H., Barry, A.J., Azari, B., Zheng, Q., Beddow, T., Zhao, B., and Tobey, I.G. (2023). Targeting AAV vectors to the central nervous system by engineering capsid\u2013receptor interactions that enable crossing of the blood\u2013brain barrier. PLoS Biol., 21.","DOI":"10.1371\/journal.pbio.3002112"},{"key":"ref_164","doi-asserted-by":"crossref","unstructured":"Ghauri, M.S., and Ou, L. (2023). AAV Engineering for Improving Tropism to the Central Nervous System. Biology, 12.","DOI":"10.3390\/biology12020186"},{"key":"ref_165","doi-asserted-by":"crossref","unstructured":"O\u2019Carroll, S.J., Cook, W.H., and Young, D. (2021). AAV Targeting of Glial Cell Types in the Central and Peripheral Nervous System and Relevance to Human Gene Therapy. Front. Mol. Neurosci., 13.","DOI":"10.3389\/fnmol.2020.618020"},{"key":"ref_166","doi-asserted-by":"crossref","unstructured":"Brown, D., Altermatt, M., Dobreva, T., Chen, S., Wang, A., Thomson, M., and Gradinaru, V. (2021). Deep Parallel Characterization of AAV Tropism and AAV-Mediated Transcriptional Changes via Single-Cell RNA Sequencing. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.730825"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1001\/jama.2024.28666","article-title":"Eladocagene Exuparvovec for Aromatic L-Amino Acid Decarboxylase Deficiency","volume":"333","author":"Golikeri","year":"2025","journal-title":"JAMA"},{"key":"ref_168","doi-asserted-by":"crossref","unstructured":"Daci, R., and Flotte, T.R. (2024). Delivery of Adeno-Associated Virus Vectors to the Central Nervous System for Correction of Single Gene Disorders. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25021050"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1038\/s41392-025-02336-2","article-title":"AAV for gene therapy drives a nephrotoxic response via NF\u03baB in kidney organoids","volume":"10","author":"Gupta","year":"2025","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1016\/S1474-4422(10)70254-4","article-title":"Gene delivery of AAV2-neurturin for Parkinson\u2019s disease: A double-blind, randomised, controlled trial","volume":"9","author":"Marks","year":"2010","journal-title":"Lancet Neurol."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"1698","DOI":"10.1212\/WNL.0b013e3182904faa","article-title":"Safety\/feasibility of targeting the substantia nigra with AAV2-neurturin in Parkinson patients","volume":"80","author":"Bartus","year":"2013","journal-title":"Neurology"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1016\/S0140-6736(16)00082-9","article-title":"Calcium upregulation by percutaneous administration of gene therapy in patients with cardiac disease (CUPID 2): A randomised, multinational, double-blind, placebo-controlled, phase 2b trial","volume":"387","author":"Greenberg","year":"2016","journal-title":"Lancet"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1016\/S1474-4422(23)00313-7","article-title":"Safety and efficacy of gene replacement therapy for X-linked myotubular myopathy (ASPIRO): A multinational, open-label, dose-escalation trial","volume":"22","author":"Shieh","year":"2023","journal-title":"Lancet Neurol."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1001\/jamaneurol.2020.1484","article-title":"Assessment of Systemic Delivery of rAAVrh74.MHCK7.micro-dystrophin in Children With Duchenne Muscular Dystrophy: A Nonrandomized Controlled Trial","volume":"77","author":"Mendell","year":"2020","journal-title":"JAMA Neurol."},{"key":"ref_175","unstructured":"Doxzen, K., Cornetta, K., Hongeng, S., Kityo, C., Mahlangu, J., Makani, J., and Mathews, V. (2022). Accelerating Global Access to Gene Therapies: Case Studies from Low- and Middle-Income Countries, World Economic Forum."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1038\/d41586-024-02310-y","article-title":"Make gene therapies more available by manufacturing them in lower-income nations","volume":"631","author":"Harlow","year":"2024","journal-title":"Nature"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1002\/ana.25450","article-title":"Magnetic resonance imaging\u2013guided phase 1 trial of putaminal AADC gene therapy for Parkinson\u2019s disease","volume":"85","author":"Christine","year":"2019","journal-title":"Ann. Neurol."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1007\/s00701-024-06028-8","article-title":"Taking the knife to neurodegeneration: A review of surgical gene therapy delivery to the CNS","volume":"166","author":"Perera","year":"2024","journal-title":"Acta Neurochir."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"4653","DOI":"10.1038\/s41467-025-60000-3","article-title":"Optimized AAV capsids for basal ganglia diseases show robust potency and distribution","volume":"16","author":"Leib","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"eadr2531","DOI":"10.1126\/scitranslmed.adr2531","article-title":"An AAV variant selected through NHP screens robustly transduces the brain and drives secreted protein expression in NHPs and mice","volume":"17","author":"Tecedor","year":"2025","journal-title":"Sci. Transl. Med."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"6602","DOI":"10.1038\/s41467-024-50555-y","article-title":"Systematic multi-trait AAV capsid engineering for efficient gene delivery","volume":"15","author":"Eid","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_182","doi-asserted-by":"crossref","unstructured":"Wang, Z., Li, H., Xu, X., Sun, Z., He, R., Zhang, L., Yu, M., Wang, S., Hu, C., and Liu, L. (2026). Novel Engineered AAV Variants Demonstrate Superior Blood-Brain Barrier Penetration and Safety in Non-Human Primates. bioRxiv.","DOI":"10.64898\/2026.03.29.713052"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.omtm.2022.01.013","article-title":"Characterization of AAV-mediated dorsal root ganglionopathy","volume":"24","author":"Buss","year":"2022","journal-title":"Mol. Ther.\u2014Methods Clin. Dev."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"e70447","DOI":"10.1002\/jmv.70447","article-title":"Revolution of AAV in Drug Discovery: From Delivery System to Clinical Application","volume":"97","author":"Yin","year":"2025","journal-title":"J. Med. Virol."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1038\/sj.mt.6300322","article-title":"A Hybrid Vector System Expands Adeno-associated Viral Vector Packaging Capacity in a Transgene-independent Manner","volume":"16","author":"Ghosh","year":"2008","journal-title":"Mol. Ther."},{"key":"ref_186","first-page":"611","article-title":"Adeno-associated Virus (AAV) Dual Vector Strategies for Gene Therapy Encoding Large Transgenes","volume":"90","author":"McClements","year":"2017","journal-title":"Yale J. Biol. Med."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1002\/emmm.201302948","article-title":"Effective delivery of large genes to the retina by dual AAV vectors","volume":"6","author":"Trapani","year":"2014","journal-title":"EMBO Mol. Med."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/978-1-4939-9139-6_2","article-title":"Design of AAV Vectors for Delivery of Large or Multiple Transgenes","volume":"Volume 1950","author":"Castle","year":"2019","journal-title":"Adeno-Associated Virus Vectors"},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1089\/hgtb.2013.212","article-title":"Dual adeno-associated virus vectors result in efficient in vitro and in vivo expression of an oversized gene, MYO7A","volume":"25","author":"Dyka","year":"2014","journal-title":"Hum. Gene Ther. Methods"},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"6811","DOI":"10.1093\/hmg\/ddv386","article-title":"Improved dual AAV vectors with reduced expression of truncated proteins are safe and effective in the retina of a mouse model of Stargardt disease","volume":"24","author":"Trapani","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1038\/gt.2014.8","article-title":"Efficient gene delivery to the cone-enriched pig retina by dual AAV vectors","volume":"21","author":"Colella","year":"2014","journal-title":"Gene Ther."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"15009","DOI":"10.1038\/mtm.2015.9","article-title":"A comparison of AAV strategies distinguishes overlapping vectors for efficient systemic delivery of the 6.2\u2009kb Dysferlin coding sequence","volume":"2","author":"Pryadkina","year":"2015","journal-title":"Mol. Ther.\u2014Methods Clin. Dev."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"6578","DOI":"10.1038\/s41467-023-42386-0","article-title":"mRNA trans-splicing dual AAV vectors for (epi)genome editing and gene therapy","volume":"14","author":"Riedmayr","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1089\/hum.2022.138","article-title":"Immune Responses and Immunosuppressive Strategies for Adeno-Associated Virus-Based Gene Therapy for Treatment of Central Nervous System Disorders: Current Knowledge and Approaches","volume":"33","author":"Prasad","year":"2022","journal-title":"Hum. Gene Ther."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"3220","DOI":"10.1016\/j.ymthe.2024.07.016","article-title":"A systematic review of immunosuppressive protocols used in AAV gene therapy for monogenic disorders","volume":"32","author":"Vrellaku","year":"2024","journal-title":"Mol. Ther."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1089\/hum.2013.238","article-title":"Intracerebral Administration of Adeno-Associated Viral Vector Serotype rh.10 Carrying Human SGSH and SUMF1 cDNAs in Children with Mucopolysaccharidosis Type IIIA Disease: Results of a Phase I\/II Trial","volume":"25","author":"Tardieu","year":"2014","journal-title":"Hum. Gene Ther."},{"key":"ref_197","doi-asserted-by":"crossref","unstructured":"Kaiser, V.M., and Gonzalez-Cordero, A. (2025). Organoids\u2013the future of pre-clinical development of AAV gene therapy for CNS disorders. Gene Ther.","DOI":"10.1038\/s41434-025-00527-8"},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"113506","DOI":"10.1016\/j.expneurol.2020.113506","article-title":"TREM2 overexpression rescues cognitive deficits in APP\/PS1 transgenic mice by reducing neuroinflammation via the JAK\/STAT\/SOCS signaling pathway","volume":"336","author":"Ruganzu","year":"2021","journal-title":"Exp. Neurol."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"2949","DOI":"10.1038\/npp.2014.164","article-title":"Upregulation of TREM2 Ameliorates Neuropathology and Rescues Spatial Cognitive Impairment in a Transgenic Mouse Model of Alzheimer\u2019s Disease","volume":"39","author":"Jiang","year":"2014","journal-title":"Neuropsychopharmacology"},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"111438","DOI":"10.1016\/j.mad.2021.111438","article-title":"TREM2, microglia, and Alzheimer\u2019s disease","volume":"195","author":"Qin","year":"2021","journal-title":"Mech. Ageing Dev."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1016\/j.jmb.2017.04.004","article-title":"TREM2-Ligand Interactions in Health and Disease","volume":"429","author":"Kober","year":"2017","journal-title":"J. Mol. Biol."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1016\/j.cell.2020.05.003","article-title":"The Physiology, Pathology, and Potential Therapeutic Applications of the TREM2 Signaling Pathway","volume":"181","author":"Deczkowska","year":"2020","journal-title":"Cell"},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1089\/hgtb.2015.140","article-title":"Expressing Transgenes That Exceed the Packaging Capacity of Adeno-Associated Virus Capsids","volume":"27","author":"Chamberlain","year":"2016","journal-title":"Hum. Gene Ther. Methods"},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"2609","DOI":"10.1016\/j.xphs.2021.03.024","article-title":"Manufacturing Challenges and Rational Formulation Development for AAV Viral Vectors","volume":"110","author":"Srivastava","year":"2021","journal-title":"J. Pharm. Sci."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1089\/hgtb.2016.188","article-title":"Improving the Quality of Adeno-Associated Viral Vector Preparations: The Challenge of Product-Related Impurities","volume":"28","year":"2017","journal-title":"Hum. Gene Ther. Methods"},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1038\/s41434-021-00311-4","article-title":"Rapid characterization of adeno-associated virus (AAV) gene therapy vectors by mass photometry","volume":"29","author":"Wu","year":"2022","journal-title":"Gene Ther."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"3311","DOI":"10.1002\/bit.28524","article-title":"Development of a novel purification method for AAV vectors using tangential flow filtration","volume":"120","author":"Miyaoka","year":"2023","journal-title":"Biotech. Bioeng."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"2100219","DOI":"10.1002\/biot.202100219","article-title":"Novel anion exchange membrane chromatography method for the separation of empty and full adeno-associated virus","volume":"17","author":"Hejmowski","year":"2022","journal-title":"Biotechnol. J."},{"key":"ref_209","doi-asserted-by":"crossref","unstructured":"Kowshik, N.C.S.S., and Singh, P. (2025). Advancing AAV vector manufacturing: Challenges, innovations, and future directions for gene therapy. Front. Mol. Med., 5.","DOI":"10.3389\/fmmed.2025.1709095"},{"key":"ref_210","doi-asserted-by":"crossref","unstructured":"Duzenli, O.F., and Aslanidi, G. (2025). Consecutive Affinity and Ion-Exchange Chromatography for AAV9 Vectors Purification. Biomedicines, 13.","DOI":"10.3390\/biomedicines13020361"},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"1268","DOI":"10.1016\/j.tibtech.2023.04.002","article-title":"Challenges in scaling up AAV-based gene therapy manufacturing","volume":"41","author":"Jiang","year":"2023","journal-title":"Trends Biotechnol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/13\/5668\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T03:46:27Z","timestamp":1782272787000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/13\/5668"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,23]]},"references-count":211,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["ijms27135668"],"URL":"https:\/\/doi.org\/10.3390\/ijms27135668","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,23]]}}}