Targeted and heritable changes to the worm genome made easy

Specific and heritable changes introduced in the genome of the roundworm Caenorhabditis elegans using a short RNA fragment to guide a nuclease to the site intended for modification is reported in a study published this week in Nature Methods.

C. elegans is a popular model system to study development and neurobiology since the developmental fate of each of its 959 cells has been mapped, and it is transparent and easy to grow. However, manipulating its genome in a precise manner, in particular in its germ cells, has been challenging.

John Calarco and colleagues adapt a genome engineering system, Clustered Regulatory Interspaced Short Palindromic Repeats (CRISPR), to target specific breaks in worm DNA. The CRISPR system uses a short guide RNA to target the nuclease Cas9; the enzyme then introduces breaks in the DNA and imperfect repair at the targeted site leads to mutations that often destroy the function of the gene.Calarco and colleagues report that the CRISPR/Cas system effectively works in the worm, both in somatic and in germ cells.