Thread by @Prosser_Lab

Our preprint on PTBP, alternative splicing, and ASOs for @cureSYNGAP1 is now out @NatureComms!

nature.com/articles/s4146…

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https://twitter.com/Prosser_Lab/status/1549386115638894592

As a refresher, we mapped the neuronal splicing regulator PTBP2 for its binding and splicing across human cortex and iPSC-Neurons, and used these maps to guide a therapeutic ASO splice switching strategy to rescue SYNGAP1 haploinsufficiency.

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The major add from the preprint is new ASO testing in multiple SYNGAP1 patient-derived neurons, where we show that PTBP2 disrupting ASOs can improve SYNGAP1 splicing and rescue its impaired expression.

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This work was a large collaborative effort across our ENDD team, including @lab_davidson and @EAHellerPhD. It was also nicely complemented by a recent study from @xczhang11, giving us confidence in this mechanism and approach.

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