In vivo delivery of CRISPR-Cas9 genome editing components for therapeutic applications

Since its mechanism discovery in 2012 and the first application for mammalian genome editing in 2013, CRISPRCas9 has revolutionized the genome engineering field and created countless opportunities in both basic science and translational medicine. The first clinical trial of CRISPR therapeutics was initiated in 2016, which employed ex vivo CRISPR-Cas9 edited PD-1 knockout T cells for the treatment of non-small cell lung cancer. So far there have been dozens of clinical trials registered on ClinicalTrials.gov in regard to using the CRISPR-Cas9 genome editing as the main intervention for therapeutic applications; however, most of these studies use ex vivo genome editing approach, and only a few apply the in vivo editing strategy. Compared to ex vivo editing, in vivo genome editing bypasses tedious procedures related to cell isolation, maintenance, selection, and transplantation. It is also applicable to a wide range of diseases and disorders. The main obstacles to the successful translation of in vivo therapeutic genome editing include the lack of safe and efficient delivery system and safety concerns resulting from the off-target effects. In this review, we highlight the therapeutic applications of in vivo genome editing mediated by the CRISPR-Cas9 system. Following a brief introduction of the history, biology, and functionality of CRISPR-Cas9, we showcase a series of exemplary studies in regard to the design and implementation of in vivo genome editing systems that target the brain, inner ear, eye, heart, liver, lung, muscle, skin, immune system, and tumor. Current challenges and opportunities in the field of CRISPR-enabled therapeutic in vivo genome editing are also discussed.

Automated summary

Since its discovery in 2012, CRISPRCas9 has revolutionized the field of genome engineering and has shown great potential in basic science and translational medicine. The majority of clinical trials using CRISPR-Cas9 for therapeutic applications focus on ex vivo genome editing, with only a few utilizing in vivo editing strategies. In vivo genome editing bypasses tedious procedures and can be applied to a wide range of diseases and disorders. However, the lack of safe and efficient delivery systems and concerns about off-target effects pose challenges to successful translation. This review highlights the therapeutic applications of in vivo genome editing mediated by the CRISPR-Cas9 system and discusses current challenges and opportunities in the field.