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  • Perspective
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Therapeutic strategies for fragile X syndrome and implications for other gene-silencing disorders

Nature Genetics volume 57, pages 1812–1822 (2025)Cite this article

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Abstract

Gene-silencing disorders, of which fragile X syndrome (FXS) is the most prevalent, are diseases caused by a blockade of gene transcription, usually due to DNA hypermethylation. FXS is a common form of inherited intellectual disability and autism. Unlike most hereditary diseases driven by mutations within the protein-coding region of a gene, FXS is caused by a trinucleotide expansion in the 5′-untranslated region of the FMR1 gene, leading to hypermethylation and transcriptional silencing. Modeling FXS with human pluripotent stem cells offers a clinically relevant platform to study disease mechanisms and explore potential therapies through reactivating FMR1 expression by genetic and epigenetic means or through drug screening. This Perspective reviews the various cellular models and therapeutic strategies proposed over the past decade, highlighting their potential to advance the treatment of FXS. We also discuss the benefits and challenges of gene activation therapies, drawing comparisons with other gene-silencing disorders, including imprinting diseases and X-linked disorders.

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Fig. 1: The molecular basis of the different states leading to FXS.
Fig. 2: Molecular strategies to affect expansion or methylation of FMR1.
Fig. 3: Screening approaches for the identification of small molecules and candidate genes to target FXS.
Fig. 4: Gene reactivation strategies to target different types of gene-silencing diseases.

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References

  1. Ng, S. B. et al. Exome sequencing identifies the cause of a Mendelian disorder. Nat. Genet. 42, 30–35 (2010).

    Article  PubMed  CAS  Google Scholar 

  2. Zhang, F. & Lupski, J. R. Non-coding genetic variants in human disease. Hum. Mol. Genet. 24, R102–R110 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Zoghbi, H. Y. & Beaudet, A. L. Epigenetics and human disease. Cold Spring Harb. Perspect. Biol. 8, a019497 (2016).

    Google Scholar 

  4. Malik, I., Kelley, C. P., Wang, E. T. & Todd, P. K. Molecular mechanisms underlying nucleotide repeat expansion disorders. Nat. Rev. Mol. Cell Biol. 22, 589–607 (2021).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Eggermann, T. et al. Imprinting disorders. Nat. Rev. Dis. Primers 9, 33 (2023).

    Article  PubMed  Google Scholar 

  6. Tabolacci, E. & Chiurazzi, P. Epigenetics, fragile X syndrome and transcriptional therapy. Am. J. Med. Genet. A 161A, 2797–2808 (2013).

    Article  PubMed  Google Scholar 

  7. Hagerman, R. J. et al. Fragile X syndrome. Nat. Rev. Dis. Primers 3, 17065 (2017).

    Article  PubMed  Google Scholar 

  8. Coffee, B. et al. Incidence of fragile X syndrome by newborn screening for methylated FMR1 DNA. Am. J. Hum. Genet. 85, 503–514 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Richter, J. D. & Zhao, X. The molecular biology of FMRP: new insights into fragile X syndrome. Nat. Rev. Neurosci. 22, 209–222 (2021).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Dahlhaus, R. Of men and mice: modeling the fragile X syndrome. Front. Mol. Neurosci. 11, 41 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  11. Vershkov, D. & Benvenisty, N. Human pluripotent stem cells in modeling human disorders: the case of fragile X syndrome. Regen. Med. 12, 53–68 (2017).

    Article  PubMed  CAS  Google Scholar 

  12. Kumari, D. et al. Identification of fragile X syndrome-specific molecular markers in human fibroblasts: a useful model to test the efficacy of therapeutic drugs. Hum. Mutat. 35, 1485–1494 (2014).

    Article  PubMed  CAS  Google Scholar 

  13. Brasa, S. et al. Reciprocal changes in DNA methylation and hydroxymethylation and a broad repressive epigenetic switch characterize FMR1 transcriptional silencing in fragile X syndrome. Clin. Epigenetics 8, 15 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  14. Schwartz, P. H. et al. Neural progenitor cells from an adult patient with fragile X syndrome. BMC Med. Genet. 6, 2 (2005).

    Article  PubMed  PubMed Central  Google Scholar 

  15. Bhattacharyya, A. et al. Normal neurogenesis but abnormal gene expression in human fragile X cortical progenitor cells. Stem Cells Dev. 17, 107–117 (2008).

    CAS  Google Scholar 

  16. Castrén, M. et al. Altered differentiation of neural stem cells in fragile X syndrome. Proc. Natl Acad. Sci. USA 102, 17834–17839 (2005).

    Article  PubMed  PubMed Central  Google Scholar 

  17. Obernier, K. & Alvarez-Buylla, A. Neural stem cells: origin, heterogeneity and regulation in the adult mammalian brain. Development 146, dev156059 (2019).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Bar, S. & Benvenisty, N. Human pluripotent stem cells: derivation and applications. Nat. Rev. Mol. Cell Biol. https://doi.org/10.1038/S41580-020-00309-7 (2020).

  19. Bhattacharyya, A. & Zhao, X. Human pluripotent stem cell models of fragile X syndrome. Mol. Cell. Neurosci. 73, 43–51 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  20. Mor-Shaked, H. & Eiges, R. Modeling fragile X syndrome using human pluripotent stem cells. Genes 7, 77 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  21. Vershkov, D., Ben-Hur, T. & Benvenisty, N. in Fragile X Syndrome: from Genetics to Targeted Treatment (eds Willemsen, R. & Kooy, R. F.) 103–121 (Academic, 2017).

  22. Burton, A. & Torres-Padilla, M. E. Epigenome dynamics in early mammalian embryogenesis. Nat. Rev. Genet. https://doi.org/10.1038/s41576-025-00831-4 (2025).

  23. Eiges, R. et al. Developmental study of fragile X syndrome using human embryonic stem cells derived from preimplantation genetically diagnosed embryos. Cell Stem Cell 1, 568–577 (2007).

    Article  PubMed  CAS  Google Scholar 

  24. Urbach, A., Bar-Nur, O., Daley, G. Q. & Benvenisty, N. Differential modeling of fragile X syndrome by human embryonic stem cells and induced pluripotent stem cells. Cell Stem Cell 6, 407–411 (2010).

    CAS  Google Scholar 

  25. Bar-Nur, O., Russ, H. A., Efrat, S. & Benvenisty, N. Epigenetic memory and preferential lineage-specific differentiation in induced pluripotent stem cells derived from human pancreatic islet beta cells. Cell Stem Cell 9, 17–23 (2011).

    Article  PubMed  CAS  Google Scholar 

  26. Hu, B. Y. et al. Neural differentiation of human induced pluripotent stem cells follows developmental principles but with variable potency. Proc. Natl Acad. Sci. USA 107, 4335–4340 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. Halevy, T., Czech, C. & Benvenisty, N. Molecular mechanisms regulating the defects in fragile X syndrome neurons derived from human pluripotent stem cells. Stem Cell Reports 4, 37–46 (2015).

    Article  PubMed  CAS  Google Scholar 

  28. Kang, Y. et al. A human forebrain organoid model of fragile X syndrome exhibits altered neurogenesis and highlights new treatment strategies. Nat. Neurosci. 24, 1377–1391 (2021).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. Lee, A., Xu, J., Wen, Z. & Jin, P. Across dimensions: developing 2D and 3D human iPSC-based models of fragile X syndrome. Cells 11, 1725 (2022).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. Gunapala, K. M. et al. Ascorbic acid ameliorates molecular and developmental defects in human-induced pluripotent stem cell and cerebral organoid models of fragile X syndrome. Int. J. Mol. Sci. 25, 12718 (2024).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Huang, Y. et al. Research progress, challenges, and breakthroughs of organoids as disease models. Front. Cell Dev. Biol. 9, 740574 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  32. Shivram, H., Cress, B. F., Knott, G. J. & Doudna, J. A. Controlling and enhancing CRISPR systems. Nat. Chem. Biol. 17, 10–19 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  33. Park, C. Y. et al. Reversion of FMR1 methylation and silencing by editing the triplet repeats in fragile X iPSC-derived neurons. Cell Rep. 13, 234–241 (2015).

    Article  PubMed  CAS  Google Scholar 

  34. Xie, N. et al. Reactivation of FMR1 by CRISPR/Cas9-mediated deletion of the expanded CGG-repeat of the fragile X chromosome. PLoS ONE 11, e0165499 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  35. Fischer, L. A., Khan, S. A. & Theunissen, T. W. Induction of human naïve pluripotency using 5i/L/A medium. Methods Mol. Biol. 2416, 13–28 (2022).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. Lee, H. G. et al. Site-specific R-loops induce CGG repeat contraction and fragile X gene reactivation. Cell 186, 2593–2609 (2023).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  37. Williams, K., Christensen, J. & Helin, K. DNA methylation: TET proteins—guardians of CpG islands? EMBO Rep. 13, 28–35 (2012).

    Article  CAS  Google Scholar 

  38. Groh, M. & Gromak, N. Out of balance: R-loops in human disease. PLoS Genet. 10, e1004630 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  39. Smeets, H. J. M. et al. Normal phenotype in two brothers with a full FMR1 mutation. Hum. Mol. Genet. 4, 2103–2108 (1995).

    Article  PubMed  CAS  Google Scholar 

  40. Liu, X. S. et al. Rescue of fragile X syndrome neurons by DNA methylation editing of the FMR1 gene. Cell 172, 979–992 (2018).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. Haenfler, J. M. et al. Targeted reactivation of FMR1 transcription in fragile X syndrome embryonic stem cells. Front. Mol. Neurosci. 11, 282 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  42. Tseng, E., Tang, H. T., AlOlaby, R. R., Hickey, L. & Tassone, F. Altered expression of the FMR1 splicing variants landscape in premutation carriers. Biochim Biophys. Acta Gene Regul. Mech. 1860, 1117–1126 (2017).

    Article  PubMed  CAS  Google Scholar 

  43. Shah, S. et al. Antisense oligonucleotide rescue of CGG expansion dependent FMR1 mis-splicing in fragile X syndrome restores FMRP. Proc. Natl Acad. Sci. USA 120, e2302534120 (2023).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Colak, D. et al. Promoter-bound trinucleotide repeat mRNA drives epigenetic silencing in fragile X syndrome. Science 343, 1002–1005 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  45. Paluszkiewicz, S. M., Martin, B. S. & Huntsman, M. M. Fragile X syndrome: the GABAergic system and circuit dysfunction. Dev. Neurosci. 33, 349–364 (2011).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. Berry-Kravis, E. et al. Mavoglurant in fragile X syndrome: results of two randomized, double-blind, placebo-controlled trials. Sci. Transl. Med. 8, 321ra325 (2016).

    Article  Google Scholar 

  47. Grabb, M. C. & Potter, W. Z. CNS trial failures: using the fragile X syndrome-mGluR5 drug target to highlight the complexities of translating preclinical discoveries into human trials. J. Clin. Psychopharmacol. 42, 234–237 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  48. Kurosaki, T. et al. Loss of the fragile X syndrome protein FMRP results in misregulation of nonsense-mediated mRNA decay. Nat. Cell Biol. 23, 40–48 (2021).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Kumari, D. et al. High-throughput screening to identify compounds that increase fragile X mental retardation protein expression in neural stem cells differentiated from fragile X syndrome patient-derived induced pluripotent stem cells. Stem Cells Transl. Med. 4, 800–808 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  50. Vershkov, D. et al. FMR1 reactivating treatments in fragile X iPSC-derived neural progenitors in vitro and in vivo. Cell Rep. 26, 2531–2539 (2019).

    Article  PubMed  CAS  Google Scholar 

  51. Hunt, J. F. V. et al. High throughput small molecule screen for reactivation of FMR1 in fragile X syndrome human neural cells. Cells 11, 69 (2022).

    Article  CAS  Google Scholar 

  52. Hagemann, S., Heil, O., Lyko, F. & Brueckner, B. Azacytidine and decitabine induce gene-specific and non-random DNA demethylation in human cancer cell lines. PLoS ONE 6, e17388 (2011).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  53. Thota, S., Oganesian, A., Azab, M. & Griffiths, E. A. Role of cedazuridine/decitabine in the management of myelodysplastic syndrome and chronic myelomonocytic leukemia. Future Oncol. 17, 2077–2087 (2021).

    Article  PubMed  CAS  Google Scholar 

  54. Vershkov, D., Yilmaz, A., Yanuka, O., Nielsen, A. L. & Benvenisty, N. Genome-wide screening for genes involved in the epigenetic basis of fragile X syndrome. Stem Cell Reports 17, 1048–1058 (2022).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  55. Mulley, J. C. et al. FRAXE and mental retardation. J. Med. Genet. 32, 162–169 (1995).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  56. Gecz, J., Gedeon, A. K., Sutherland, G. R. & Mulley, J. C. Identification of the gene FMR2, associated with FRAXE mental retardation. Nat. Genet. 13, 105–108 (1996).

    Article  PubMed  CAS  Google Scholar 

  57. Youings, S. A. et al. FRAXA and FRAXE: the results of a five-year survey. J. Med. Genet. 37, 415–421 (2000).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  58. Schulz, J. B. et al. Diagnosis and treatment of Friedreich ataxia: a European perspective. Nat. Rev. Neurol. 5, 222–234 (2009).

    Article  PubMed  Google Scholar 

  59. Mosbach, V. & Puccio, H. A multiple animal and cellular models approach to study frataxin deficiency in Friedreich ataxia. Biochim. Biophys. Acta Mol. Cell Res. 1871, 119809 (2024).

    Article  PubMed  CAS  Google Scholar 

  60. Schreiber, A. M., Li, Y., Chen, Y. H., Napierala, J. S. & Napierala, M. Selected histone deacetylase inhibitors reverse the Frataxin transcriptional defect in a novel Friedreich’s ataxia induced pluripotent stem cell-derived neuronal reporter system. Front. Neurosci. 16, 836476 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  61. Lyst, M. J. & Bird, A. Rett syndrome: a complex disorder with simple roots. Nat. Rev. Genet. 16, 261–274 (2015).

    Article  PubMed  CAS  Google Scholar 

  62. Gold, W. A. et al. Rett syndrome. Nat. Rev. Dis. Primers 10, 84 (2024).

    Article  PubMed  Google Scholar 

  63. Qian, J. et al. Multiplex epigenome editing of MECP2 to rescue Rett syndrome neurons. Sci. Transl. Med. 15, eadd4666 (2023).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  64. Pescatore, A., Esposito, E., Draber, P., Walczak, H. & Ursini, M. V. NEMO regulates a cell death switch in TNF signaling by inhibiting recruitment of RIPK3 to the cell death-inducing complex II. Cell Death Dis. 7, e2346 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  65. Parrish, J. E., Scheuerle, A. E., Lewis, R. A., Levy, M. L. & Nelson, D. L. Selection against mutant alleles in blood leukocytes is a consistent feature in incontinentia pigmenti type 2. Hum. Mol. Genet. 5, 1777–1783 (1996).

    Article  PubMed  CAS  Google Scholar 

  66. Kenwrick, S. et al. Survival of male patients with incontinentia pigmenti carrying a lethal mutation can be explained by somatic mosaicism or Klinefelter syndrome. Am. J. Hum. Genet. 69, 1210–1217 (2001).

    Article  PubMed  CAS  Google Scholar 

  67. Fusco, F., Fimiani, G., Tadini, G., Michele, D. & Ursini, M. V. Clinical diagnosis of incontinentia pigmenti in a cohort of male patients. J. Am. Acad. Dermatol. 56, 264–267 (2007).

    Article  PubMed  Google Scholar 

  68. Reik, W. & Walter, J. Genomic imprinting: parental influence on the genome. Nat. Rev. Genet. 2, 21–32 (2001).

    Article  PubMed  CAS  Google Scholar 

  69. Buiting, K., Williams, C. & Horsthemke, B. Angelman syndrome — insights into a rare neurogenetic disorder. Nat. Rev. Neurol. 12, 584–593 (2016).

    Article  PubMed  CAS  Google Scholar 

  70. Wakeling, E. L. Silver–Russell syndrome. Arch. Dis. Child. 96, 1156–1161 (2011).

    Article  PubMed  Google Scholar 

  71. Cassidy, S. B., Schwartz, S., Miller, J. L. & Driscoll, D. J. Prader–Willi syndrome. Genet. Med. 14, 10–26 (2012).

    Article  PubMed  CAS  Google Scholar 

  72. Docherty, L. E. et al. Clinical presentation of 6q24 transient neonatal diabetes mellitus (6q24 TNDM) and genotype–phenotype correlation in an international cohort of patients. Diabetologia 56, 758–762 (2013).

    Article  PubMed  CAS  Google Scholar 

  73. Choufani, S., Shuman, C. & Weksberg, R. Beckwith–Wiedemann syndrome. Am. J. Med. Genet. C Semin. Med. Genet. 154C, 343–354 (2010).

    Article  PubMed  CAS  Google Scholar 

  74. Huang, H. S. et al. Topoisomerase inhibitors unsilence the dormant allele of Ube3a in neurons. Nature 481, 185–191 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  75. Vihma, H. et al. Ube3a unsilencer for the potential treatment of Angelman syndrome. Nat. Commun. 15, 5558 (2024).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  76. Wolter, J. M. et al. Cas9 gene therapy for Angelman syndrome traps Ube3a-ATS long non-coding RNA. Nature 587, 281–284 (2020).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  77. Schmid, R. S. et al. CRISPR/Cas9 directed to the Ube3a antisense transcript improves Angelman syndrome phenotype in mice. J. Clin. Invest. 131, e142574 (2021).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  78. Rohm, D. et al. Activation of the imprinted Prader–Willi syndrome locus by CRISPR-based epigenome editing. Cell Genom. 5, 100770 (2025).

    CAS  Google Scholar 

  79. Wang, S. E. & Jiang, Y.-H. Novel epigenetic molecular therapies for imprinting disorders. Mol. Psychiatry 28, 3182–3193 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  80. Garber, K. B., Visootsak, J. & Warren, S. T. Fragile X syndrome. Eur. J. Hum. Genet. 16, 666–672 (2008).

    Article  PubMed  CAS  Google Scholar 

  81. Rodriguez-Revenga, L. et al. Penetrance of FMR1 premutation associated pathologies in fragile X syndrome families. Eur. J. Hum. Genet. 17, 1359–1362 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  82. Tassone, F. et al. Elevated levels of FMR1 mRNA carrier males: a new mechanism of involvement in the fragile-X syndrome. Am. J. Hum. Genet. 66, 6–15 (2000).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  83. Tassone, F. et al. Elevated FMR1 mRNA in premutation carriers is due to increased transcription. RNA 13, 555–562 (2007).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  84. Kraan, C. M., Godler, D. E. & Amor, D. J. Epigenetics of fragile X syndrome and fragile X-related disorders. Dev. Med. Child Neurol. 61, 121–127 (2019).

    Article  PubMed  Google Scholar 

  85. Landy, S. J. & Donnai, D. Incontinentia pigmenti (Bloch–Sulzberger syndrome). J. Med. Genet. 30, 53–59 (1993).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  86. Vaghani, U. P. et al. Bloch–Sulzberger syndrome: a rare X-linked dominant genetic disorder in a newborn. Cureus 15, e48823 (2023).

    PubMed  PubMed Central  Google Scholar 

  87. Prasasya, R., Grotheer, K. V., Siracusa, L. D. & Bartolomei, M. S. Temple syndrome and Kagami–Ogata syndrome: clinical presentations, genotypes, models and mechanisms. Hum. Mol. Genet. 29, R107–R116 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  88. Baena, N. et al. Novel 14q32.2 paternal deletion encompassing the whole DLK1 gene associated with Temple syndrome. Clin. Epigenetics 16, 62 (2024).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Acknowledgements

We thank all members of the Azrieli Center for Stem Cells and Genetic Research for critical reading of the manuscript. N.B. was supported by the Azrieli Foundation, the Rosetrees Trust, the Israel Science Foundation (no. 2054/22) and the ISF–Israel Precision Medicine Partnership Program (no. 3605/21). A.G is a PhD fellow of the Neubauer Foundation. N.B. is the Herbert Cohn Chair in Cancer Research.

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  1. The Azrieli Center for Stem Cells and Genetic Research, Department of Genetics, the Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel

    Aseel Gadban, Keith M. Gunapala & Nissim Benvenisty

  2. Department of Biomedicine, University of Basel, Basel, Switzerland

    Keith M. Gunapala & Verdon Taylor

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  2. Keith M. Gunapala
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A.G., K.M.G., V.T. and N.B. conceived the main ideas presented in this Perspective. A.G. drafted the manuscript with contribution by K.M.G., V.T. and N.B. N.B. supervised the submission of the Perspective and secured funding.

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Correspondence to Keith M. Gunapala, Verdon Taylor or Nissim Benvenisty.

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Gadban, A., Gunapala, K.M., Taylor, V. et al. Therapeutic strategies for fragile X syndrome and implications for other gene-silencing disorders. Nat Genet 57, 1812–1822 (2025). https://doi.org/10.1038/s41588-025-02255-6

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