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Comment by sva_ | Hacker News Reader

> Lee’s research team “stumbled” on the discovery after investigating a “gene desert”, a stretch of DNA on chromosome 21 that does not code for proteins, which has previously been linked to IBD and other autoimmune diseases. Writing in Nature, they describe how they found a section of DNA that behaves like a volume control for nearby genes. This “enhancer” was seen only in immune cells called macrophages where it boosted a gene called ETS2 and ramped up the risk of IBD.

> Through gene editing experiments, the scientists showed that ETS2 is central to the inflammatory behaviour of macrophages and their ability to damage the bowel in IBD.

Sounds like a win for CRISPR-Cas9

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Partly. The "model" for inflammation that confirms a causal relation doesn't look like it's ever been used before.

> To directly confirm that ETS2 was causal, we used CRISPR–Cas9 to delete the 1.85 kb enhancer region in primary human monocytes before culturing these cells with inflammatory ligands, including TNF (a pro-inflammatory cytokine), prostaglandin E2 (a pro-inflammatory lipid) and Pam3CSK4 (a TLR1/2 agonist) (TPP model; Fig. 1d and Extended Data Fig. 2a–c). This model was designed to mimic chronic inflammation16, and better resembles disease macrophages than classical IFNγ-driven or IL-4-driven models17 (Extended Data Fig. 2).

i.e., gene editing (by whatever means) is not really a win any more than changing bits in memory is. The win comes from having an in-vitro model that replicates the in-vivo disease, or from correctly identifying the relevant genes (e.g., here ETS2 is the furthest gene considered, and could easily have been excluded).

> i.e., gene editing (by whatever means) is not really a win any more than changing bits in memory is. The win comes from having an in-vitro model that replicates the in-vivo disease

I take your point, but this would have been a challenging, expensive endeavor before CRISPR-Cas9. Likely, the perturbation would not have been done in the same paper as the announcement of the locus due to the challenge of deletion work before CRISPR-Cas systems became readily available

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