CRISPR/Cas-Based Therapy Development for Rare Genetic Diseases: From Shakedown to Maiden Voyage

The long held curiosity about how to correct a variety of human diseases and defects, as well as  the quest to address disturbing and obscure solution to misfortune chance of extra chromosomes in rare diseases such as Down syndrome has deem the light of scientist's search to the field of gene therapy. The discovery of the Clustered Regularly-Interspaced Short Palindromic Repeats (CRISPR), the mechanism of the CRISPR-based prokaryotic adaptive immune system (CRISPR-associated system, Cas), and its repurposing into a potent gene editing tool has revolutionized the field of molecular biology and generated excitement for new and improved gene therapies. Additionally, these advances in genome editing with programmable nucleases have opened up new avenues for multiple applications, from basic research to clinical therapy. However, there are still many unknowns in the therapy development for rare diseases based on CRISPR/Cas technology. But with the field developing at a staggering pace, it is unclear how well current cutting-edge technology in terms of off-target effects, efficiencies of delivery, and of cell-autonomous correction will be addressed in the near future. Herein, highlight of history and basic mechanisms of the CRISPR/Cas9 system and its application in rare genetic diseases, lessons learned from past human gene therapy efforts are done. The challenges, ethical issues, and future prospects of CRISPR-based systems for human research are also discussed.