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Aron Jaffe

@jaffeab.bsky.social

SVP @ curie.bio; Former SVP Head of Research @chromamedicine; EIR @ThirdRockV; Reg Med, uBiome group leader/Resp DA co-lead @NovartisScience. Opinions my own.

Posts Replies Media

Aron Jaffe @jaffeab.bsky.social · 06/04/2025

First game of the season with the boy. Never gets old.

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Aron Jaffe @jaffeab.bsky.social · 10/02/2025

This work was led by the BlueSky-less Fred Tremblay. Fred’s scientific rigor and unflappable leadership style truly drove this program. Congratulations mon ami to you and the entire team! 9/9

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Aron Jaffe @jaffeab.bsky.social · 10/02/2025

Our human PCSK9-targeting epigenetic editor is fully cross-reactive against cyno PCSK9, & we demonstrated that a single administration led to rapid and sustained, 90% reduction of PCSK9 protein, resulting in a clinically meaningful 70% reduction in LDL-C in non-human primates 7/9

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Aron Jaffe @jaffeab.bsky.social · 10/02/2025

Not only was this methylation-driven silencing durable in a homeostatic liver, but both silencing and methylation were fully maintained during liver regeneration, indicating durability through cell division in vivo! 6/9

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Aron Jaffe @jaffeab.bsky.social · 10/02/2025

We confirmed that mRNA/gRNA encoding our human PCSK9-targeting epigenetic editor packaged into an LNP was able to reduce circulating PCSK9 protein 98% for a year after a SINGLE ADMINISTRATION in a human PCSK9 transgenic mouse! 5/9

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Aron Jaffe @jaffeab.bsky.social · 10/02/2025

We designed an mRNA-based #epigeneticeditor: DNA-binding domain fused to a DNA methyl-transferase domain & a transcriptional repressor domain which, together w/ human PCSK9-targeted gRNA, deeply & specifically methylated & silenced PCSK9 in primary human hepatocytes in vitro 4/9

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Aron Jaffe @jaffeab.bsky.social · 10/02/2025

This work was led by the BlueSky-less Fred Tremblay. Fred’s scientific rigor and unflappable leadership style truly drove this program. Congratulations mon ami to you and the entire team! 9/9

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Aron Jaffe @jaffeab.bsky.social · 10/02/2025

Our human PCSK9-targeting epigenetic editor is fully cross-reactive against cyno PCSK9, and we demonstrated that a single administration led to rapid and sustained, 90% reduction of PCSK9 protein, resulting in a clinically meaningful 70% reduction in LDL-C 7/9

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Aron Jaffe @jaffeab.bsky.social · 10/02/2025

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Aron Jaffe @jaffeab.bsky.social · 10/02/2025

We confirmed that mRNA/gRNA encoding our human PCSK9-targeting epigenetic editor packaged into an LNP was able to reduce circulating PCSK9 protein by 98% for a year after a SINGLE ADMINISTRATION in a human PCSK9 transgenic mouse! 5/9

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Aron Jaffe @jaffeab.bsky.social · 10/02/2025

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