Biomedical engineers at Duke University have used a CRISPR/Cas9 genetic engineering technique to turn off a gene that regulates cholesterol levels in adult mice, leading to reduced blood cholesterol levels and gene repression lasting for six months after a single treatment.
This marks the first time researchers have delivered CRISPR/Cas9 repressors for targeted therapeutic gene silencing in adult animal models.
The CRISPR/Cas9 system is based on an antiviral defense mechanism in bacteria in which the Cas9 enzyme recognizes the viral DNA sequences of previous infections and cuts up invading DNA during re-infection.
Researchers have engineered the CRISPR/Cas9 system to not only locate and cut specific sequences of DNA, but to also turn on or off the expression of targeted genes without making permanent changes to the DNA sequence.
While this CRISPR/Cas9 repressor technique has emerged as a robust tool for disrupting gene regulation in cell culture models, it had not yet been adapted for delivery to adult animals for applications such as gene therapy.
The Duke Researchers develop an approach to efficiently package and deliver the CRISPR/Cas9 repressor system to mice. They tested their delivery system by silencing Pcsk9, a gene that regulates cholesterol levels.
While several drugs have been developed to treat high cholesterol and cardiovascular disease by blocking the activity of Pcsk9, this new approach would prevent Pcsk9 from being made.
