June 11, 2015

A “CRISPR” way to study disease

Using revolutionary CRISPR technology, Vanderbilt investigators have developed a fast and simple method to simultaneously turn off multiple genes in order to study complex diseases.

by Henry H. Ong

Human diseases often result from complex genetic interactions. A common way to study these interactions is to simultaneously turn off multiple genes, preferably with temporal and spatial precision. However, current methods for this approach, called multiplex conditional mutagenesis, take a large amount of time and resources.

Wenbiao Chen, Ph.D., and colleagues have developed a faster and simpler method. Reporting last month in Genetics, they employed the CRISPR/Cas9 system – a revolutionary technology that greatly accelerates gene manipulation – to perform multiplex conditional mutagenesis in a common human disease model – the zebrafish.

By tailoring the two components of the system, cas9 and guide RNA, to be tissue-specific and inducible, they showed liver-specific mutagenesis of insulin receptor genes in just one generation resulting in impaired glucose homeostasis. They also showed retinal-specific mutagenesis of the ascl1a gene leading to abnormal photoreceptor regeneration in the eye.

This technique can potentially be a valuable tool for advancing our understanding of the genetic basis of human diseases.

The research was supported in part by grants from the National Institutes of Health (DK088686, EY024354) and from the American Diabetes Association.

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