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Neuro-oncology

Promising results for antisense RNA therapy in mouse models of diffuse midline glioma

Nature Reviews Neurology volume 19, page 386 (2023)Cite this article

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A translational study in mice demonstrates the feasibility of targeting RNA by using antisense technology to selectively target an oncogenic variant of histone 3.3 (H3.3) that is implicated in some types of high-grade glioma occurring mainly in paediatric populations. Although histone deacetylase inhibitors (notably panobinostat) can reverse some downstream effects of this oncogenic variant and are currently under investigation in this setting, more-specific and more-effective treatments for these rapidly lethal (5-year survival < 1%) cancers are urgently needed.

In their initial CRISPR–Cas9 gene-knockout experiments using single-guide RNA targeting, Zhang et al. confirmed that H3.3K27M is essential for tumour growth: gene knockout reduced tumour cell growth in patient-derived DIPG neurospheres. In mouse orthotopic xenograft models of DIPG, gene knockout delayed tumour formation and prolonged survival.

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References

Original article

  • Zhang, Q. et al. Antisense oligonucleotide therapy for H3.3K27M diffuse midline glioma. Sci. Transl. Med. 15, eadd8280 (2023)

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  1. Nature Reviews Neurology http://www.nature.com/nrneurol/

    Caroline Barranco

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  1. Caroline Barranco
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Correspondence to Caroline Barranco.

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Barranco, C. Promising results for antisense RNA therapy in mouse models of diffuse midline glioma. Nat Rev Neurol 19, 386 (2023). https://doi.org/10.1038/s41582-023-00829-8

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  • DOI: https://doi.org/10.1038/s41582-023-00829-8

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