Splicing to Save Memory

The rapid development of CRISPR gene editing technologies in mammalian systems has massively enhanced the capabilities of modern molecular biology to specifically alter an organism’s DNA. The CRISPR system utilizes components of a natural bacterial immune process. The main enzyme, Cas9, uses a guide RNA to direct it to a site of genomic DNA, where it cuts both strands. The DNA cut is resolved by one of two natural DNA double stranded break processes: non-homologous end joining, or homology directed repair. If homology directed repair is desired, a double stranded DNA repair template must also be introduced with Cas9 and the guide RNA. Through the non-homologous end joining pathway, the CRISPR-Cas9 system is most efficient at generating small insertions or deletions at the cut site. Currently, CRISPR-Cas9 is an actively used and powerful tool in the laboratory space, providing researchers with a new method to affect gene expression in a specific manner. Although it is an impressive new tool, CRISPR-Cas9 does have its limitations. In particular, off-target editing effects and the limited number of efficiently made mutations are major concerns that impede its clinical development.

A few weeks ago, a group from the Broad Institute described a new version of gene editing, termed prime editing, which circumvents many of the challenges of the CRISPR-Cas9 system...