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Gene therapy

An epigenome editing approach induces durable silencing of Pcsk9

Nature Reviews Cardiology volume 21, page 279 (2024)Cite this article

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A new approach to modify the epigenome can lead to durable silencing of Pcsk9 in mice, thereby reducing plasma LDL-cholesterol levels, according to a study published in Nature. “Epigenome editing should represent a safer therapeutic alternative to conventional genome editing, as it does not induce DNA breaks that can, in turn, cause chromosomal translocations and other genotoxic effects,” explains lead investigator Angelo Lombardo.

Epigenome editing (or epi-editing) uses programmable editors that are based on naturally occurring transcriptional repressors. “In previous studies, we identified a combination of epigenetic effector domains that, when configured into epigenetic editors termed engineered transcriptional repressors (ETRs), were able to induce efficient and durable gene silencing in cell lines,” says Lombardo. Moreover, he explains that these epi-editors can also induce gene silencing when they are transiently delivered into a cell.

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  • Brandts, J. & Ray, K. K. Novel and future lipid-modulating therapies for the prevention of cardiovascular disease. Nat. Rev. Cardiol. 20, 600–616 (2023)

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  1. Nature Reviews Cardiology http://www.nature.com/nrcardio/

    Irene Fernández-Ruiz

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  1. Irene Fernández-Ruiz
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Correspondence to Irene Fernández-Ruiz.

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Fernández-Ruiz, I. An epigenome editing approach induces durable silencing of Pcsk9. Nat Rev Cardiol 21, 279 (2024). https://doi.org/10.1038/s41569-024-01011-3

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  • DOI: https://doi.org/10.1038/s41569-024-01011-3

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