SoylentNews

takyon [soylentnews.org] writes:

CRISPR study reduces cholesterol in mice without "editing" DNA [newatlas.com]

Rather than hacking away with genetic scissors, recent work [newatlas.com] has instead used CRISPR to temporarily turn certain genes on and off through epigenetic modulation. In that vein, the new study developed a CRISPR-Cas9 repressor system that can silence a gene called Pcsk9 [newatlas.com], which regulates cholesterol levels. The Duke researchers managed to package this system and deliver it into the livers of adult mice.

"We previously used these same types of tools to turn genes on and off in cultured cells, and we wanted to see if we could also deliver them to animal models with an approach that is relevant for gene therapy," says Charles Gersbach, lead researcher on the study. "We wanted to change the genes in a way that would have a therapeutic outcome, and Pcsk9 is a useful proof-of-concept given its role regulating cholesterol levels, which in turn affect health issues like heart disease."

The researchers started with a Cas9 enzyme taken from the bacteria species Staphylococcus aureus, and to keep it from making cuts to the target DNA, they created a "dead" version dubbed dCas9. This was bundled with a KRAB protein that silences gene expression, and the combination was then packaged inside adeno-associated viral (AAV) vectors – viruses that are engineered to carry the active ingredients to the right DNA target.

In their tests, the Duke researchers delivered the system to adult mice, where it activated in their livers. Compared to a control group that had simple saline injections, the Pcsk9 genes in the test mice were successfully repressed and the animals' cholesterol levels dropped as a result. Better yet, the effects of a single treatment lasted six months.

RNA-guided transcriptional silencing in vivo with S. aureus CRISPR-Cas9 repressors [nature.com] (open, DOI: 10.1038/s41467-018-04048-4) (DX [doi.org])

Related: CRISPR Used to Reduce Tissue Inflammation and Damage [soylentnews.org]
CRISPR Used to Epigenetically Treat Diseases in Mice [soylentnews.org]

Original Submission