Salk Institute researchers have used CRISPR/Cas9 therapy to suppress aging, enhance health and extend life span in mice.
Above – This image shows two mice of the same age with progeria. The larger and healthier mouse on the left received the gene therapy, while the mouse on the right did not. Credit: Salk Institute
They were able to suppress the accelerated aging observed in mice with Hutchinson-Gilford progeria syndrome, a rare genetic disorder that also afflicts humans. This treatment provides important insight into the molecular pathways involved in accelerated aging, as well as how to reduce toxic proteins via gene therapy.
The researchers utilized the CRISPR/Cas9 system to deliver the gene therapy into the cells of the progeria mouse model expressing Cas9. An adeno-associated virus (AAV) was injected containing two synthetic guide RNAs and a reporter gene. The guide RNA ushers the Cas9 protein to a specific location on the DNA where it can make a cut to render lamin A and progerin nonfunctional, without disrupting lamin C. The reporter helps researchers track the tissues that were infected with the AAV.
Two months after the delivery of the therapy, the mice were stronger and more active, with improved cardiovascular health. They showed decreased degeneration of a major arterial blood vessel and delayed onset of bradycardia (an abnormally slow heart rate)—two issues commonly observed in progeria and old age. Overall, the treated progeria mice had activity levels similar to normal mice, and their life span increased by roughly 25 percent.
They plan to improve the efficiency of the distribution of gene therapy to tissues. They believe this will further increase life span improvement.
There is no cure for progeria in human. Symptoms are managed and complications are treated as they arise.
Abstract – Single-dose CRISPR–Cas9 therapy extends lifespan of mice with Hutchinson–Gilford progeria syndrome
Hutchinson–Gilford progeria syndrome (HGPS) is a rare lethal genetic disorder characterized by symptoms reminiscent of accelerated aging. The major underlying genetic cause is a substitution mutation in the gene coding for lamin A, causing the production of a toxic isoform called progerin. Here we show that reduction of lamin A/progerin by a single-dose systemic administration of adeno-associated virus-delivered CRISPR–Cas9 components suppresses HGPS in a mouse model.