CRISPR-Cas9 technology comprises an emerging class of tailorable, robust gene editing agents for altering mutations in genetic diseases like sickle diseases and sensorineural hearing loss. However, several hurdles in delivery, editing efficiency, immunogenicity and off-target ratio have significantly constrained the clinical applications. It is reported that the CRISPR-Cas9 ribonucleoprotein (RNP) or its mRNA transiently delivered by synthetic nanoparticles had fewer off-target ratio, but more desirable editing efficiency compared to those by viral vectors. Exosomes are biological membrane vesicles with a size range of 30-150nm comparable to the synthetic nanoparticles but superior in biocompatibility, targeting ability and stability. Encapsulation of pharmaceutically active substances into exosomes such as anti-cancer drugs, antibodies, enzymes, has been reported to be of great significance in addressing multiple clinical issues and promising in targeted gene editing. However, how to effectively encapsulate gene editing agents into exosomes for robust but safe gene editing events in vivo still remains an open question. Therefore, in this project, we propose to use and compare RNP or its mRNA in editing the desirable genes in Alzheimer’s disease (AD) and sensorineural hearing loss (SNHL), in order to illuminate the future of exosome-mediated gene editing for neurodegenerative diseases. Herein, the development and characterization of single guide RNA and delivery of CRISPR/Cas9 as the functional complexes in vitro, the key for the future gene editing in vivo, is envisaged as a rational and promising goal to reach for a novel gene therapy strategy for AD and SNHL.