Shinya Ya­mana­ka No­bel Prize

In 2006, Shinya Ya­mana­ka shook stem cell re­search with his dis­cov­ery that ma­ture cells can be con­vert­ed in­to stem cells, re­liev­ing a long­stand­ing po­lit­i­cal-eth­i­cal block­age and throw­ing open med­ical re­search on every­thing from curb­ing eye de­gen­er­a­tion to or­gan print­ing.

But that process still has pit­falls, in­clud­ing in risk and scal­a­bil­i­ty, and some re­searchers are ex­plor­ing an­oth­er way first hint­ed at years ago: new tech­nol­o­gy to con­vert ma­ture cells di­rect­ly in­to oth­er ma­ture cells with­out the com­plex and time-con­sum­ing process of first mak­ing them in­to stem cells.

One of those com­pa­nies, Mo­gri­fy, just raised $16 mil­lion in Se­ries A fi­nanc­ing to bring its over­all fund­ing to over $20 mil­lion since its Feb­ru­ary launch. Led by CEO Dar­rin Dis­ley, the fund­ing will help ex­pand their new base in Cam­bridge to a 60-strong staff and push for­ward their di­rect-con­ver­sion ap­proach to cell ther­a­py through re­search and li­cens­ing. In­vestors in­clude Park­walk Ad­vi­sors and Ahren In­no­va­tion Cap­i­tal.

They list po­ten­tial ap­pli­ca­tions as treat­ments for mus­cu­loskele­tal and au­to-im­mune dis­or­ders, can­cer im­munother­a­py, and ther­a­pies for oc­u­lar and res­pi­ra­to­ry dis­eases. For ex­am­ple, you could use it re­gen­er­ate car­ti­lage in arthri­tis pa­tients.

“If you could take a cell from one part of the body and turn it in­to any oth­er cell at any oth­er stage of de­vel­op­ment for an­oth­er part of the body, you ef­fec­tive­ly have the Holy Grail of re­gen­er­a­tive med­i­cine,” Dis­ley told Labiotech.eu in April.

Mo­gri­fy’s ad­van­tage over the Ya­mana­ka method called in­duced pluripo­tent stem cells (iPS), is that in the­o­ry it can be more scal­able and avoid the prob­lems as­so­ci­at­ed with iPS. These in­clude in­sta­bil­i­ties aris­ing from the in­duced im­ma­ture state and an in­creased risk of can­cer if any pluripo­tent cells re­main in the body.

The con­cept be­hind Mo­gri­fy ac­tu­al­ly pre­dates, by near­ly 19 years, Ya­mana­ka’s dis­cov­ery, which fast won him the 2012 No­bel Prize in Med­i­cine. A 2017 Na­ture study on “trans­d­if­fer­en­ti­a­tion,” as the process is called, of fi­brob­lasts in­to car­diac tis­sue traced the idea to a 1987 find­ing that a mas­ter gene reg­u­la­tor could con­vert mice fi­brob­lasts in­to skele­tal mus­cle.

The prob­lem though, ac­cord­ing to Mo­gri­fy, is that most cur­rent ef­forts re­ly on an ex­haust­ing guess-and-check process. With hun­dreds of cell types and an even greater num­ber of tran­scrip­tion fac­tors — the pro­gram that re­codes the cell — find­ing the right fac­tor for the right cell can be like a cus­to­di­an with a jan­gling, un­marked key ring try­ing to get in­to a build­ing with thou­sands of locks.

Mo­gri­fy’s key tech is a com­put­er mod­el they say can pre­dict the right com­bi­na­tion. The sci­en­tists be­hind the plat­form pub­lished a 2016 study in Na­ture ap­ply­ing the mod­el to 173 hu­man cell types and 134 tis­sues.

Be­fore Mo­gri­fy, Dis­ley led the Cam­bridge-based gene-edit­ing com­pa­ny Hori­zon Dis­cov­ery.