For those also curious, Yamanaka factors are specific genes that turn specialized cells (e.g. skin, hair) into induced pluripotent stem cells (iPSCs) which can turn into any other type of cell.
This is a big deal because you can generate lots of stem cells to make full organs[1] or reverse aging (maybe? they say you just turn the cell back younger, not all the way to stem cells).
You can also do better disease modeling/drug testing: if you get skin cells from someone w/ a genetic kidney disease, you can turn those cells into the iPSCs, then into kidney cells which will exhibit the same kidney disease because it’s genetic. You can then better understand how the [kidney disease] develops and how various drugs affect it.
So, it’s good to have ways to produce lots of these iPSCs. According to the article, SOTA was <1% of cells converted into iPSCs, whereas the GPT suggestions caused a 50x improvement to 33% of cells converted. That’s quite huge!, so hopefully this result gets verified. I would guess this is true and still a big deal, but concurrent work got similar results.
Too bad about the tumors. Turns out iPSCs are so good at turning into other cells, that they can turn into infinite cells (ie cancer). iPSCs were used to fix spinal cord injuries (in mice) which looked successful for 112 days, but then a follow up study said [a different set of mice also w/ spinal iPSCs] resulted in tumors.
My current understanding is this is caused by the method of delivering these genes (ie the Yamanaka factors) through retrovirus which
is a virus that uses RNA as its genomic material. Upon infection with a retrovirus, a cell converts the retroviral RNA into DNA, which in turn is inserted into the DNA of the host cell.
which I’d guess this is the method the Retro Biosciences uses.
Induced pluripotent stem cells were first generated by Shinya Yamanaka and Kazutoshi Takahashi at Kyoto University, Japan, in 2006.[1] They hypothesized that genes important to embryonic stem cell (ESC) function might be able to induce an embryonic state in adult cells. They chose twenty-four genes previously identified as important in ESCs and used retroviruses to deliver these genes to mouse fibroblasts. The fibroblasts were engineered so that any cells reactivating the ESC-specific gene, Fbx15, could be isolated using antibiotic selection.
Upon delivery of all twenty-four factors, ESC-like colonies emerged that reactivated the Fbx15 reporter and could propagate indefinitely. To identify the genes necessary for reprogramming, the researchers removed one factor at a time from the pool of twenty-four. By this process, they identified four factors, Oct4, Sox2, cMyc, and Klf4, which were each necessary and together sufficient to generate ESC-like colonies under selection for reactivation of Fbx15.
Sox2-17 enhanced episomal OKS MEF reprogramming by a striking 150 times, giving rise to high-quality miPSCs that could generate all-iPSC mice with up to 77% efficiency
For human cells, up to 9% (if I’m understanding this part correctly).
SOX2-17 gave rise to 56 times more TRA1-60+ colonies compared with WT-SOX2: 8.9% versus 0.16% overall reprogramming efficiency.
So seems like you can do wildly different depending on the setting (mice, humans, bovine, etc), and I don’t know what the Retro folks were doing, but does make their result less impressive.
Thinking through it more, Sox2-17 (they changed 17 amino acids from Sox2 gene) was your linked paper’s result, and Retro’s was a modified version of factors Sox AND KLF. Would be cool if these two results are complementary.
For those also curious, Yamanaka factors are specific genes that turn specialized cells (e.g. skin, hair) into induced pluripotent stem cells (iPSCs) which can turn into any other type of cell.
This is a big deal because you can generate lots of stem cells to make full organs[1] or reverse aging (maybe? they say you just turn the cell back younger, not all the way to stem cells).
You can also do better disease modeling/drug testing: if you get skin cells from someone w/ a genetic kidney disease, you can turn those cells into the iPSCs, then into kidney cells which will exhibit the same kidney disease because it’s genetic. You can then better understand how the [kidney disease] develops and how various drugs affect it.
So, it’s good to have ways to produce lots of these iPSCs. According to the article, SOTA was <1% of cells converted into iPSCs, whereas the GPT suggestions caused a 50x improvement to 33% of cells converted.
That’s quite huge!, so hopefully this result gets verified.I would guess this is true and still a big deal, but concurrent work got similar results.Too bad about the tumors. Turns out iPSCs are so good at turning into other cells, that they can turn into infinite cells (ie cancer). iPSCs were used to fix spinal cord injuries (in mice) which looked successful for 112 days, but then a follow up study said [a different set of mice also w/ spinal iPSCs] resulted in tumors.
My current understanding is this is caused by the method of delivering these genes (ie the Yamanaka factors) through retrovirus which
which I’d guess this is the method the Retro Biosciences uses.
I also really loved the story of how Yamanaka discovered iPSCs:
These organs would have the same genetics as the person who supplied the [skin/hair cells] so risk of rejection would be lower (I think)
I don’t think that’s right, see https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(23)00402-2
You’re right! Thanks
For Mice, up to 77%
For human cells, up to 9% (if I’m understanding this part correctly).
So seems like you can do wildly different depending on the setting (mice, humans, bovine, etc), and I don’t know what the Retro folks were doing, but does make their result less impressive.
(Still impressive and interesting of course, just not literally SOTA.)
Thinking through it more, Sox2-17 (they changed 17 amino acids from Sox2 gene) was your linked paper’s result, and Retro’s was a modified version of factors Sox AND KLF. Would be cool if these two results are complementary.