In Vivo Applications of CRISPR-Based Genome Editing in the Retina

Abstract

The rapidly evolving CRISPR-based genome editing technology is bringing revolutionary changes to the entirety of the life sciences. In this mini-review, we summarize the recent progress of in vivo applications of CRISPR genome editing in retinal studies. Non-viral and viral vector mediated delivery have been developed for temporary or persistent expression of CRISPR components in retinal cells. Although in theory CRISPR-based genome editing can correct a large number of mutant genes responsible for a variety of inherited retinal disorders (IRDs), precise gene modification relies on homology-directed repair (HDR)-the efficiency of which is not currently high enough for meaningful benefit. Development of CRISPR-based treatment for retinal diseases thus far has been mainly focused on gene knock-out or gene deletion in which the highly efficient non-homologous end joining (NHEJ) repair pathway is involved. Therapeutic benefits have been achieved in a few rodent models of retinal diseases following CRISPR treatment. The in vivo applications of CRISPR have also facilitated studies of gene function in the retina. As off-target events and immune responses are still the major concerns, continuous development of safer CRISPR genome editing systems is prerequisite for its clinical applications.

Keywords: AAV vector; CRISPR; gene therapy; genome editing; photoreceptors; retinal degeneration.

Figure 1

Overview of the mechanisms of CRISPR-based genome editing and its applications for treating retinal diseases. (A). The mechanisms and patterns of CRISPR genome editing utilized in existing retinal studies, with black region indicating normal genomic DNA, gray region indicating the PAM motif, and red, orange and pink regions indicating different CRISPR-targeted sequences. (B). Past and future applications of CRISPR genome editing for treating retinal diseases.