Fig. 5: In vivo reversibility of the effects of the PCSK9 EE using a PCSK9 epigenetic activator. | Nature Medicine

Fig. 5: In vivo reversibility of the effects of the PCSK9 EE using a PCSK9 epigenetic activator.

From: A potent epigenetic editor targeting human PCSK9 for durable reduction of low-density lipoprotein cholesterol levels

Fig. 5: In vivo reversibility of the effects of the PCSK9 EE using a PCSK9 epigenetic activator.

a, Schematic outline of PCSK9 silencing in mice using a PCSK9 EE (PCSK9-EE), followed at more than 100 d by treatment with a PCSK9 activator (dCas-Tet). Illustration was created with BioRender. b, Circulating PCSK9 protein levels after a single administration of an LNP formulation with dCas-Tet in PCSK9-Tg previously treated with PCSK9-EE to silence PCSK9. Results are shown as mean ± s.d. (n = 5 mice). c, Effect of a single administration of LNP formulation with dCas-Tet in PCSK9-Tg mice previously treated with PCSK9-EE to silence PCSK9 on CpG methylation levels at 56 d after dCas-Tet treatment. CpG location (first row) and the methylation percentage (0–100%) of each CpG dinucleotide at the PCSK9 locus in cells expressing PCSK9 (liver hepatocyte; second row) or not expressing PCSK9 (neuron; third row). CpG methylation profiles for all analyzed samples are shown for c.

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