You are unique - Does your gene editing treatment need to be too?

Many diseases are caused by genetic mutations. Small mutations can cause certain cancers, some cases of blindness, influence heart disease, and many other pathologies. A new and powerful technology called CRISPR-Cas9 aims to correct for these genetic mutations by cutting out a piece of malfunctioning DNA, and replacing it with a piece of genetic material that functions correctly. Biologists first discovered CRISPR-Cas9 in bacteria. Through careful study, scientists are making strides in order to use the system to edit human DNA and treat genetic diseases.

A recent study, however, suggests researchers should exercise caution as they begin to use the technique in humans. DNA is made up of a series of what are called bases. There are four bases, called A, T, G and C. These bases sit in a specific order and give rise to each person’s genetic code. However, there is a good amount of variation in the order of the bases between different individuals. Stuart Orkin and his team looked at thirty genes known to cause disease. They found that half of the time, the defective gene in question had big enough differences in the order of the bases that it could have interfered with the CRISPR-Cas9 system. Additionally, the gene editing system occasionally targeted a different and perfectly normal piece of DNA. The researchers emphasize that as tests of these promising technologies begin in humans, careful analysis of each person’s individual genome will be necessary.

Our experts Kelsey Tyssowski, a graduate student in Harvard’s Biology and Biomedical Science program and Charlie Longtine a graduate student in the Molecular and Cellular Biology both note that Stuart Orkin and his team used a computer simulation, and we can’t be sure of how the research will apply in real cells. This research highlights the complexity of the differences between individuals, as well as some of the essential steps of moving from a treatment that works in bacteria to a treatment that works for humans.

Acknowledgements: Many thanks to Kelsey Tyssowski a graduate student in Harvard’s Biology and Biomedical Science program and Charlie Longtine a graduate student in the Molecular and Cellular Biology

Managing Correspondent: Emily Kerr

Original Research Article: Human genetic variation alters CRISPR-Cas9 on- and off-targeting specificity at therapeutically implicated loci

Media Coverage: Time for a Tailor