Skip to main content
Home » Rare Diseases » Gene editing innovations targeting multiple variants for rare diseases

Patrick T. Harrison, PhD

Professor of Molecular Physiology, Department of Physiology, University College Cork

A Cork-based research team is developing groundbreaking gene editing strategies that target multiple variants to tackle rare diseases.

At the genetic level, we each have many, small variants in our DNA that make each of us unique. Occasionally, one of these variants disrupts the instructions for making an essential protein in our body. This is the cause of many rare diseases such as cystic fibrosis (CF), which affects about 2,000 people in Ireland. So, if some of these variants cause a disease, can you target them directly to develop new treatments?

Gene editing for CF

In 2012, a technique known as gene editing was successfully used for the first time to target the most common DNA variant that causes CF. “By editing the DNA sequence of a disease-causing variant, you can restore the instructions to make a functional protein,” notes Patrick Harrison, Professor of Molecular Physiology at University College Cork, who led this breakthrough study.

However, as CF can be caused by any 1 of over 500 variants, the use of gene editing strategies that only target one variant at a time would mean developing potentially hundreds of approaches just for one disease.

By editing the DNA sequence of a disease-causing
variant, you can restore the instructions
to make a functional protein.

Gene editing for multiple variants

“The question is whether we can find strategies where you can edit small clusters of variants in the same region of DNA,” says Harrison. “We are developing techniques that could do this for three or four such clusters. If we could then translate this to the clinic, it could restore production of a functional protein for most people with CF.”

Harrison adds: “This is important, as many of the variants we are targeting do not respond to the recently approved CF ‘modulator’ drugs. In Ireland, that’s about 20% of people with CF; potentially 50% of people with CF globally.”

Expanding gene editing applications

CF advances may translate to other lung disorders or rare diseases affecting different organs. Harrison elaborates that the field is progressing swiftly. Merely three months ago, the first gene editing medicine gained approval for sickle cell disease, marking a remarkable breakthrough. However, further research is imperative to extend this technology’s reach to numerous other diseases — and enhancing accessibility must be prioritised.

Research in the Harrison Lab is supported by Science Foundation Ireland, CF Trust (UK) and CF Foundation (USA).

Next article