Meesmann’s corneal dystrophy is caused by the presence of a mutant copy of a gene that codes for a structural protein in corneal epithelium. People who carry this mutant gene develop cysts on the cornea which rupture and cause irritation and loss of vision.

Most people who have corneal dystrophy also carry a healthy allele that is silenced by the dominant mutant allele. If the mutant allele was inactivated, then the healthy allele would become unsilenced and be able to build the normal protein framework in the cornea.

This is where the exciting gene editing technology called CRISPR/Cas9 comes in. The technology is based on a structure composed of two molecules. Cas9 is a protein that cuts DNA like ‘molecular scissors’ and induces a change in the sequence. The other element of the system is a piece of RNA that guides this molecular scissors to the specific gene sequence that we want to change. The aim in this case is to change the mutant allele that causes the cysts and knock it out so the healthy allele can be expressed.

crispr-cas9-at-work-data

The RNA guides the Cas9 “molecular scissors” to the mutant gene so it can make the cut and induce a sequence change

 

Mice that had the dominant human mutant gene for corneal dystrophy were injected with this Cas9 ‘molecular scissor’ construct in a study by Courtney et al (2016). After the corneal DNA of these mice was analyzed, the scientists found that nearly 40% of the mutant allele responsible for corneal dystrophy had been altered. If the molecular scissors are able to target and knock out 50% of the mutant allele, then patient’s cornea will be restored.

 

This exciting work is a pivotal stepping stone in the development of treatment for corneal dystrophy and other dominantly inherited conditions.

This article touches the surface of the findings in this paper, please read it if you wish to find out more: Courtney, D. G., et al. “CRISPR/Cas9 DNA cleavage at SNP-derived PAM enables both in vitro and in vivo KRT12 mutation-specific targeting.” Gene therapy (2016).

Other information was sourced from: yourgenome.org and cornealdystrophyfoundation.org.

Christi Smith