Mahesh Karande (Omega)

'Ex­quis­ite con­trol': Flag­ship pulls off $85M ral­ly around Omega Ther­a­peu­tic­s' clin­i­cal push for epi­ge­net­ic pro­gram­ming tech

Omega Ther­a­peu­tics be­gan, as all biotech fledg­lings in­cu­bat­ed at Flag­ship Labs do, with an off-the-wall ques­tion: Can one con­trol gene ex­pres­sion but not cre­ate the mas­sive nu­cle­ic acid se­quence changes that are cre­at­ed by gene ther­a­py and gene edit­ing?

Not long af­ter the in­ter­nal team be­gan ru­mi­nat­ing on the idea, as chief Ma­hesh Karande ex­plained at the of­fi­cial launch last Sep­tem­ber, they found an an­swer in a sem­i­nal pa­per pub­lished by Rick Young’s group at the White­head In­sti­tute. Genes and their reg­u­la­to­ry el­e­ments, he found, gen­er­al­ly re­side in loops closed off by a pair of CTCF pro­teins — neigh­bor­hoods that were lat­er named “in­su­lat­ed ge­nom­ic do­mains,” or IGDs. By send­ing reg­u­la­tor or ef­fec­tor pro­teins to dys­reg­u­lat­ed IGDs (there are more than 15,000 of them in to­tal), Omega’s pitch was to cre­ate a con­trolled epi­ge­net­ic pro­gram­ming plat­form for what Karande calls the “con­trol room of hu­man bi­ol­o­gy.”

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