MINI REVIEW article
Front. Mol. Biosci.
Sec. Molecular Diagnostics and Therapeutics
Volume 12 - 2025 | doi: 10.3389/fmolb.2025.1681647
RNA-based therapies for Neurodevelopmental Disorders: innovative tools for molecular correction
Provisionally accepted
- 1Institute of Genetics and Biophysics Adriano Buzzati-Traverso, Department of Biomedical Sciences, National Research Council (CNR), Naples, Italy
- 2Azienda Ospedaliera di Caserta Sant Anna e San Sebastiano, Caserta, Italy
- 3Maria Rosaria Maglione Foundation Onlus, Naples, Italy
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Modulation of RNA and protein expression to restore or normalize neuronal function has emerged as a powerful therapeutic strategy for neurodevelopmental disorders (NDDs) tailoring individual genetic mutations causing intellectual disability (ID), or autism spectrum disorder (ASD), or developmental epileptic encephalopathy (DEE). In recent years, diverse classes of RNA-based molecules have been developed with therapeutic potential, including antisense oligonucleotides (ASOs), antagoNATs (oligonucleotides targeting natural antisense transcripts (antagoNATs), SINEUPs (Short Interspersed Nuclear Element UP-regulating RNAs (SINEUPs), interfering RNAs (RNAi), and Exon-Specific engineering U1 small nuclear RNAs (ExSpeU1s), and small-activating RNA (saRNA). This review highlights the promising advances of these RNA-based therapeutics in addressing syndromic ID, such as Fragile X syndrome, MECP2 duplication syndrome, FOXG1-gene related Rett syndrome and Angelman syndrome, which are characterized by well-defined genetic mutations with limited treatment options. Moreover, ASD-related condition linked to mutations in CHD8 is under investigation, extending the therapeutic landscape to complex behavioral and cognitive disorders. In the same way, several DEEs caused by mutations in CDKL5, DNM1, , KCNT1, SCN1A, SCN2A, SCN8A, and UBA5 genes, which present severe pharmaco-resistant epilepsy, are increasingly becoming targets for RNA molecules that aim to restore neuronal excitability and network function. Together, these findings underscore the expanding therapeutic landscape enabled by RNA technologies, offering unprecedented specificity and flexibility for gene-targeted interventions in NDDs. As the field of RNA medicine continues to evolve across genomics and neuroscience, we aim to provide a resource for researchers and clinicians on promising innovative tools for molecular correction.
Keywords: genetic NDDs, Animal Models, RNA metabolism, Gene Expression Regulation, Haploinsufficiency, translation
Received: 07 Aug 2025; Accepted: 10 Oct 2025.
Copyright: © 2025 Drongitis, Verrillo, de Bellis and Miano. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Maria Giuseppina Miano, miano@igb.cnr.it
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.