{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T05:16:58Z","timestamp":1788412618624,"version":"build-2803163510"},"reference-count":163,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007700","name":"Carol Davila University of Medicine and Pharmacy","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007700","id-type":"DOI","asserted-by":"publisher"}]},{"id":[{"id":"https:\/\/ror.org\/04fm87419","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Genetic neurodevelopmental disorders (NDDs) encompass a heterogeneous group of conditions characterized by impaired cognitive, behavioral, and neurological development resulting from pathogenic variants affecting brain development and synaptic function. Advances in molecular genetics and next-generation sequencing have significantly expanded the understanding of the genetic architecture underlying disorders such as Rett syndrome (RTT), Fragile X syndrome (FXS), Angelman syndrome (AS), and autism spectrum disorders. Beyond these classical neurodevelopmental disorders, spinal muscular atrophy (SMA) is included as a paradigmatic example of successful RNA-based therapeutic translation. Concurrently, RNA-based therapeutics have emerged as promising precision medicine strategies capable of modulating gene expression at the transcriptional and post-transcriptional levels. These approaches include antisense oligonucleotides (ASOs), small interfering RNAs (siRNAs), messenger RNA (mRNA) therapies, RNA editing technologies, and splice-modulating agents. Recent clinical successes, particularly in spinal muscular atrophy, have demonstrated the transformative potential of RNA therapeutics in neurological disease. However, substantial challenges remain, including BBB penetration, long-term safety, immune activation, and genotype-specific variability in therapeutic response. This review summarizes current advances in RNA-based therapeutics for genetic NDDs, highlighting molecular mechanisms, disease-specific therapeutic strategies, translational progress, delivery challenges, and future directions. Overall, continued progress will depend on the integration of disease biology, rational RNA therapeutic design, and effective CNS-targeted delivery, supporting the broader implementation of precision RNA medicine for genetic neurodevelopmental disorders.<\/jats:p>","DOI":"10.3390\/ijms27177725","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T09:48:36Z","timestamp":1788256116000},"page":"7725","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["RNA-Based Therapeutics in Genetic Neurodevelopmental Disorders: Bridging Molecular Genetics and Precision Medicine"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9528-9083","authenticated-orcid":false,"given":"Ina-Ofelia","family":"Foc\u0219a","sequence":"first","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania"},{"name":"Psychiatry Research Laboratory, Prof. Dr. Alexandru Obregia Clinical Hospital of Psychiatry, 041914 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catrinel","family":"Iliescu","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Department, Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 041914 Bucharest, Romania"},{"name":"Pediatric Neurology Department, Prof. Dr. Alexandru Obregia Clinical Hospital of Psychiatry, 041914 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Pomeran","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Department, Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 041914 Bucharest, Romania"},{"name":"Pediatric Neurology Department, Prof. Dr. Alexandru Obregia Clinical Hospital of Psychiatry, 041914 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Budi\u0219teanu","sequence":"additional","affiliation":[{"name":"Psychiatry Research Laboratory, Prof. Dr. Alexandru Obregia Clinical Hospital of Psychiatry, 041914 Bucharest, Romania"},{"name":"Medical Genetics Laboratory, Victor Babes National Institute of Pathology, 050096 Bucharest, Romania"},{"name":"Department of Genetics, Faculty of Medicine, Titu Maiorescu University, 031593 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Sandu","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Department, Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 041914 Bucharest, Romania"},{"name":"Pediatric Neurology Department, Prof. Dr. Alexandru Obregia Clinical Hospital of Psychiatry, 041914 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice Denisa","family":"Dic\u0103","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Department, Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 041914 Bucharest, Romania"},{"name":"Pediatric Neurology Department, Prof. Dr. Alexandru Obregia Clinical Hospital of Psychiatry, 041914 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1697-9132","authenticated-orcid":false,"given":"Florentina Ionela","family":"Linc\u0103","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania"},{"name":"Department of Special Psychopedagogy, Faculty of Psychology and Educational Sciences, University of Bucharest, 0506578 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Mo\u021boiescu","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Department, Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 041914 Bucharest, Romania"},{"name":"Pediatric Neurology Department, Prof. Dr. Alexandru Obregia Clinical Hospital of Psychiatry, 041914 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6223-6383","authenticated-orcid":false,"given":"Diana","family":"B\u00e2rc\u0103","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Department, Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 041914 Bucharest, Romania"},{"name":"Pediatric Neurology Department, Prof. Dr. Alexandru Obregia Clinical Hospital of Psychiatry, 041914 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioana","family":"Minciu","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Department, Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 041914 Bucharest, Romania"},{"name":"Pediatric Neurology Department, Prof. Dr. Alexandru Obregia Clinical Hospital of Psychiatry, 041914 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana","family":"Craiu","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Department, Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 041914 Bucharest, Romania"},{"name":"Pediatric Neurology Department, Prof. Dr. Alexandru Obregia Clinical Hospital of Psychiatry, 041914 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viorica Elena","family":"R\u0103doi","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania"},{"name":"\u201cAlessandrescu-Rusescu\u201d National Institute for Maternal and Child Health, 20382 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.conb.2010.08.009","article-title":"The genetics of neurodevelopmental disease","volume":"21","author":"Mitchell","year":"2011","journal-title":"Curr. 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