CRISPR/Cas9 — the gene editing technology making headlines for the past 6 years — was originally part of the bacterial immune system. Bacteria protect themselves by storing snippets of DNA from viruses that have infected them before. These DNA sequences are called CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats). When bacteria detect invasive viral DNA, a CRISPR-associated protein (Cas9) goes to the CRISPR DNA sequence and helps make CRISPR RNA. This RNA matches to the invasive viral DNA, then cuts the invasive DNA, rendering the infection useless.
Cas9 can repair genes by following RNA that leads it to DNA with a genetic mutation. The Cas9 protein cuts out the mutated gene. This cut alone is enough to cure some genetic diseases. For instance, Huntington’s disease stems from too many repeats of the CAG trinucleotide. A Cas9 protein cuts out the excess copies, and the cell heals the DNA strand without having to make any changes to it. This process is called non-homologous end joining (NHEJ). (photo source)
The other gene editing process is called homology-directed repair (HDR). HDR Cas9 systems come with one extra component: a piece of donor DNA that acts as the template to fix the mutated DNA. First, the Cas9 protein cuts out the mutated gene. Then, when enzymes realize the DNA strand is broken, they grab the strand of donor DNA, stick it in the break, and stitch the strand back together. HDR is helpful for treating diseases like Duchenne muscular dystrophy. In Duchenne, some of the genetic mutations are short enough that CRISPR can quickly and easily fix them.
CRISPR is important because precisely and easily editing living cells has, until now, been beyond our grasp. This means that we could soon treat at least the 10,000 genetic disorders that stem from a single genetic mutation. As a therapeutic, CRISPR could improve and extend countless lives, and there is promise for extending these modalities to multiple mutation diseases as well.
