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Change your Genes with Stem Cells!


So researchers for the first time were evaluating the safety and reliability of the existing targeted gene correction technologies and in the process they successfully developed a new method of gene editing, TALEN-HDAdV [which I will explain later]. This new breakthrough could significantly increased gene-correction efficiency in human induced pluripotent stem cell [hiPSC]. You would have to guess that this is probably the science equivalent of finding a new function on your smartphone, while trying to work your microwave.

Genome editing is hard, it’s like being blind, stuck in a vat of jello and then told to read a chapter from War and Peace at the bottom of all of that. Did I mention in this scenario you’re blind?! TALEN-HDAdV is a combination of techniques to help sort through all that mess [hence the fancy little hyphen in the middle you might have missed when you read that jumble of words].

TALEN stands for — and this is a mouthful– Transcription activator-like effector nuclease. You can read more about how it works in genome editing here. But the simple version is, if your DNA were a 2 legged ladder [one you would have to set against a wall or something]. TALEN would break both the legs of the ladder at a specific place, then add new steps in the middle of that break, and close everything up again. The end result would be the ladder would be different and so would your genes.

HDAdV is another mouthful, it stands for Helper-Dependent Adenoviral Vectors. The roundabout way to explain that one is they are virus’ that can’t do anything without a particular helper virus. This makes them safe for genome editing since they can’t do anything without a specific trigger[in this case the helper virus]. You can read more about that here.

“The ability to precisely modify the DNA of stem cells has greatly accelerated research on human diseases and cell therapy,” says senior author Juan Carlos Izpisua Belmonte, professor in Salk’s Gene Expression Laboratory. “To successfully translate this technology into the clinic, we first need to scrutinize the safety of these modified stem cells, such as their genome stability and mutational load.”

The big change was the combination of stem cells along with the targeted genome editing technology [as in editing the stem cells genome itself]. This provides a powerful tool to model human diseases and develop potential cell replacement therapy. Although the utility of genome editing has been extensively documented, the impact of these technologies on mutational load at the whole-genome level remains unclear.

So before these kind of technologies are applied to humans, researchers must ascertain the risks of editing genes in stem cells. Even though both common gene-editing techniques have been shown to be accurate at altering the right stretch of DNA, concerns remain that the editing process could make the cells more unstable and prone to mutations in unrelated genes.

“As cells are being reprogrammed into stem cells, they tend to accumulate many mutations,” says Mo Li, a postdoctoral fellow in Belmonte’s lab and an author of the new paper. “So people naturally worry that any process you perform with these cells in vitro—including gene editing—might generate even more mutations.”

When the researchers evaluated the efficiencies of gene-targeting and gene-correction at the haemoglobin gene, HBB locus with other methods of gene editing that have been developed, they found all the methods had a similar efficiency at the gene HBB locus. In addition, the results of deep whole-genome sequencing indicated that TALEN and HDAdV could keep the patient’s genome integrated at a maximum level — meaning no or little risk of random mutation that was not desired– proving the safety and reliability of these methods.

[Loony hint: Locus, for those confused means a particular place, so HBB locus would just mean at the gene HBB, just wanted to clear that up after rereading it.]

Through integrating the advantages of TALEN- and HDAdV-mediated genome editing, researchers developed a new TALEN-HDAdV hybrid vector (talHDAdV), which can significantly increase the gene-correction efficiency in hiPSCs. Almost all the genetic mutations at the gene HBB locus can be detected by telHDAdV, which allows this new developed technology can be applied into the gene repair of different kinds of hemoglobin diseases such as sickle cell and Thalassemia.

So while I sit and wait for some X-men type — and really cool mutations — via gene editing [I would love to control the weather with my mind or even just metals, I’m not greedy]. At least we can help people who actually need it and can benefit from gene editing. Oh mind reading would be pretty cool too, although I have enough trouble reading my own.

Was the simplified version so simple it was boring? You might want the full study, which you can find —here!

Suzuki, K., Yu, C., Qu, J., Li, M., Yao, X., Yuan, T., Goebl, A., Tang, S., Ren, R., Aizawa, E., Zhang, F., Xu, X., Soligalla, R., Chen, F., Kim, J., Kim, N., Liao, H., Benner, C., Esteban, C., Jin, Y., Liu, G., Li, Y., & Izpisua Belmonte, J. (2014). Targeted Gene Correction Minimally Impacts Whole-Genome Mutational Load in Human-Disease-Specific Induced Pluripotent Stem Cell Clones Cell Stem Cell, 15 (1), 31-36 DOI: 10.1016/j.stem.2014.06.016

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