Gene editing technologies have unprecedented potential to unlock the promises of gene therapy. Clinical trials of gene editing have been collectively underway for over a decade and show that in-human use of gene editing is safe and feasible for treating diseases such as HIV, malignancies, hemoglobinopathies, inherited metabolic liver diseases, and hereditary retinal diseases.

CRISPR/Cas9, with its simpler design compared to the first generation of site-specific nucleases, is the platform of choice for therapeutic applications. However, the advent of base editors has shifted the paradigm for gene editing towards making point mutations within a target locus without the activation of potentially genotoxic double strand-breaks. Base editors have shown promising results in preclinical studies of human diseases.

Despite clinical trials, the delivery of gene editing reagents into target cells continues to pose as a major challenge. In many diseases, the diseased tissues are widely distributed, such as cystic fibrosis and Duchene muscular dystrophy, whereby in vivo delivery of gene editing reagents is necessary to treat the disease. In a small subset of diseases, such as hemoglobinopathies, ex vivo delivery is feasible as the gene modified target cells have the potential to engraft so as to replace unhealthy ones following transplantation. The articles in this collection provide detailed procedures for using viral and nonviral delivery strategies for introducing gene editing reagents into clinically relevant cells for therapeutic application.