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Genome editing of human pancreatic beta cell models: problems, possibilities and outlook – published online 03/06/2019

Figure from Balboa review

Diego Balboa, Rashmi B. Prasad, Leif Groop, Timo Otonkoski

Genome engineering technologies, in particular, Clustered Regularly Interspaced Short Palindromic Repeats-CRISPR-associated protein 9 (CRISPR-Cas9), have revolutionised the possibilities for genome manipulation. In this issue, Balboa et al ( summarise the progress and challenges in applying CRISPR-Cas9 to different human beta cell models to dissect the mechanisms behind diabetes-associated genetic variants. Genome editing can most effectively be used in induced pluripotent stem cells prior to their differentiation into beta cells. This method has the unique advantage of allowing studies in patient-derived cells. However, the functional immaturity of stem-cell derived islets is currently still a major limitation of this approach. At present, genome editing in primary human beta cells has not been possible, but new technologies may enable this in the future. Ingenious use of CRISPR-Cas9 and similar techniques will undoubtedly accelerate advances in our understanding of the interplay between type 1 diabetes and type 2 diabetes risk-associated genetic variants and their functional role in predisposing to the disease. The figure from this review is available as a downloadable slide.

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