Some villains are so tough that it might take a few heroes to take them on. β-thalassemia is just that evil, an all too common genetic disease at the worldwide level. Caused by simple mutations in the hemoglobin beta (HBB) gene, this beast is Mendelian in nature. Which makes a perfect target for CRISPR/Cas9, a duo with boundless potential, and a new unsuspecting sidekick. This story out of UC San Francisco takes an interesting twist by adding patient specific induced pluripotent stem cells (iPSCs) to the mix.
Here’s what they showed:
- iPSCs can be created from a patient’s own skin fibroblasts.
- CRISPR/Cas9 with the help of the piggyBac transposon can cure two disease causing mutations in the patient specific iPSCs.
- The cure carrying IPSCs showed full pluripotency and standard karyotypes.
- These iPSCs create the perfect source for custom made red blood cells, with no genetic content of their own and yet carrying the ‘cure’.
In terms of major concerns, off-target effects are all everyone talks about these days and the team showed the essential verification that none occurred and the whole process didn’t leave any residual footprints.
Senior author Yuet Wai Kan concludes that “Although we and others are able to differentiate iPSCs into blood cell progenitors as well as mature blood cells, the transplantation of the progenitors into mouse models to test them has so far proven very difficult. I believe it will take quite a few more years before we can apply it in a clinical setting.” Overall, this paper represents a critical step in stem cell-based gene therapy for monogenic diseases.
Look at CRISPR go in Genome Research, August 2014