Tong Wang

@twangmdphd.bsky.social

physician-scientist in the Greenleaf Lab interested in chemical biology, epigenetics, and clinically useful tests.

Personalized therapies hold tremendous promise but challenge traditional models of drug and biologic development. The @fda.gov outlines a path to market entry for products where a randomized trial is not feasible. Learn more: nej.md/4nUQdcl

Sounding Board 
"Nearly 30 years after the sequencing of the human genome, bespoke therapies are close to reality. The FDA will work as a partner and guide in ushering these therapies to market, and our regulatory strategies will evolve to match the pace of scientific advances." 

"FDA’s New Plausible Mechanism Pathway Vinay" by Prasad, M.D., M.P.H., and Martin A. Makary, M.D., M.P.H.

After leukemia treatments failed, Alyssa Tapley, at age 13, was told she would die. Then, doctors tried an experimental gene-edited therapy. She became the first human to try the treatment made possible by U.S. federal funding. Now 16, she’s cancer-free and planning her future.

We then used sequence-to-activity deep learning models, to predict effects of non-coding edits on TF binding and chromatin accessibility. We first show that a ChromBPNet model can predict the same GATA site disruption mechanism exploited by the FDA-approved Casgevy medicine, specifically in T cells:

Erythroblast ChromBPNet model predicts impact of known therapeutic CRISPR target (exagamglogene autotemcel, Casgevy) on accessibility a) Schematic of Casgevy mechanism. BCL11A represses fetal hemoglobin in adulthood. Disruption of a BCL11A enhancer reactivates fetal hemoglobin. b) Observed ATAC and predicted accessibility from ChromBPNet BCL11A intron, for T-cells (this study) and erythroblasts 48. c) Predicted accessibility for chr2 60495264: T>C edit and reference sequence in erythroblasts, along with DeepLIFT contribution scores. d) Predicted accessibility of chr2 60495267: T>C edit and reference sequence in erythroblasts. The ABE8e edit window is derived from the highest efficiency gRNA sg1620

(1st post @BlueSky) Preprint alert🚨a long thread. Cautions in the use of @nanopore sequencing to map DNA modifications: officially reported “accuracy” ≠ reliable mapping in real applications. We performed a critical assessment of nanopore sequencing (across different versions of models) for the 1/n

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