%0 Journal Article
%T Spell Checking Nature: Versatility of CRISPR/Cas9 for Developing Treatments for Inherited Disorders
%A Daria Wojtal
%A Dwi£żU. Kemaladewi
%A Elzbieta Hyatt
%A Evgueni£żA. Ivakine
%A Francesco Muntoni
%A Hernan£żD. Gonorazky
%A James Stavropoulos
%A James£żJ. Dowling
%A Kamel Mamchaoui
%A Michael£żD. Wilson
%A Roberto Mendoza-Londono
%A Sarah Abdullah
%A Sergio Pereira
%A Tatianna£żW.Y. Wong
%A Thomas Voit
%A Vincent Mouly
%A Zahra Baghestani
%A Zeenat Malam
%J Archive of "American Journal of Human Genetics".
%D 2016
%R 10.1016/j.ajhg.2015.11.012
%X Clustered regularly interspaced short palindromic repeat (CRISPR) has arisen as a frontrunner for efficient genome engineering. However, the potentially broad therapeutic implications are largely unexplored. Here, to investigate the therapeutic potential of CRISPR/Cas9 in a diverse set of genetic disorders, we establish a pipeline that uses readily obtainable cells from affected individuals. We show that an adapted version of CRISPR/Cas9 increases the amount of utrophin, a known disease modifier in Duchenne muscular dystrophy (DMD). Furthermore, we demonstrate preferential elimination of the dominant-negative FGFR3 c.1138G>A allele in fibroblasts of an individual affected by achondroplasia. Using a previously undescribed approach involving single guide RNA, we successfully removed large genome rearrangement in primary cells of an individual with an X chromosome duplication including MECP2. Moreover, removal of a duplication of DMD exons 18¨C30 in myotubes of an individual affected by DMD produced full-length dystrophin. Our findings establish the far-reaching therapeutic utility of CRISPR/Cas9, which can be tailored to target numerous inherited disorders
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4716669/