title: CRISPR-Cas9 gene editing: Delivery aspects and therapeutic potential.
abstract: The CRISPR-Cas9 gene editing system has taken the biomedical science field by storm, initiating rumors about future Nobel Prizes and heating up a fierce patent war, but also making significant scientific impact. The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR), together with CRISPR-associated proteins (Cas) are a part of the prokaryotic adaptive immune system and have successfully been repurposed for genome editing in mammalian cells. The CRISPR-Cas9 system has been used to correct genetic mutations and for replacing entire genes, opening up a world of possibilities for the treatment of genetic diseases. In addition, recently some new CRISPR-Cas systems have been discovered with interesting mechanistic variations. Despite these promising developments, many challenges have to be overcome before the system can be applied therapeutically in human patients and enabling delivery technology is one of the key challenges. Furthermore, the relatively high off-target effect of the system in its current form prevents it from being safely applied directly in the human body. In this review, the transformation of the CRISPR-Cas gene editing systems into a therapeutic modality will be discussed and the currently most realistic in vivo applications will be highlighted.
authors: Department of Pharmaceutics, Utrecht Institute of Pharmaceutical Sciences (UIPS), Utrecht University, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands.
authors: Erik
authors: E
authors: Oude Blenke
authors: Department of Pharmaceutics, Utrecht Institute of Pharmaceutical Sciences (UIPS), Utrecht University, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands.
authors: Martijn J W
authors: MJ
authors: Evers
authors: Department of Pharmaceutics, Utrecht Institute of Pharmaceutical Sciences (UIPS), Utrecht University, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands.
authors: Enrico
authors: E
authors: Mastrobattista
authors: Laboratory of Microbiology, Wageningen University, Dreijenplein 10, 6703 HB Wageningen, The Netherlands. Electronic address: john.vanderoost@wur.nl.
authors: John
authors: J
authors: van der Oost
mesh_terms: D000818:Animals; D064113:CRISPR-Cas Systems; D000072669:Gene Editing; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans
keywords: CRISPR-Cas; CRISPR-Cas9; Delivery systems; Ex vivo; Gene editing; Genome editing; In vivo; Therapeutic applications