Posted on 7 January 2021
Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.
Why is this research important: Hutchinson-Gilford progeria syndrome is a rare condition that results from just a single DNA letter mutation in one of the copies of the gene which encodes lamin A (a protein that stabilises and protects DNA). This leads to the production of progerin, an abnormal protein that causes symptoms of premature ageing and a drastically shortened lifespan. CRISPR-cas9 gene editing could theoretically be used to cut out the faulty copy of lamin A, but runs the risk of also disabling the healthy copy.
What did the researchers do: In this study, researchers modified CRISPR-cas9 to correct the predominant single letter mutation responsible for progeria, as opposed to cutting the DNA and hence disabling the gene. They then used a virus to deliver this editor to the cells of 2-week old mice with the human lamin A gene and progeria mutation.
Key takeaway(s) from this research: A single injection was associated with an increase in median lifespan from 215 to 510 days, and mice became more active. This was in spite of the fact that the mutation was only corrected in a relatively small proportion of cells (10% to 60%). This bodes well for the use of this approach to treat progeria in humans and genetic diseases more broadly. Around 50% of genetic mutations that cause disease are single-letter changes, and we already have the technology required to correct most of them.
In vivo base editing rescues Hutchinson–Gilford progeria syndrome in mice: https://doi.org/10.1038/s41586-020-03086-7