A weighty new study shows that CRISPR therapies can cut fat without cutting DNA. In a paper recently published, in the journal Science, UC San Francisco researchers describe how a modified version of CRISPR was used to ramp up the activity of certain genes and prevent severe obesity in mice with genetic mutations that predispose them to extreme weight gain. Importantly, the researchers achieved long-lasting weight control without making a single edit to the genome.
Though the human genome contains two copies of every gene in an individual, one from each parent, scientists know of at least 660 genes where a mutation in just one copy can lead to diseases, some of which are devastating. One such condition is severe obesity, which the authors of the new study used as a model to develop a new therapeutic approach for treating these disorders.
The technology in question is CRISPRa (a for activation). Developed at UCSF in the lab of Jonathan Weissman, PhD, professor of cellular and molecular pharmacology, CRISPRa differs from conventional CRISPR in that it doesn’t make cuts to the genome. It retains CRISPR’s guidance system, which can be programmed to home in on a particular DNA sequence, but replaces the molecular scissors with a volume control knob. When CRISPRa finds its target, it amplifies the activity of that gene. No edits are made.
The researchers believe they could have achieved similar results by using CRISPR to edit the genomes of these mice, but they argue that CRISPRa has a number of advantages over the standard version of the gene-editing technology.