New CRISPR technique could prevent obesity without cutting or editing a genome

An exciting new study from researchers at UC San Francisco has demonstrated how a new kind of CRISPR technique can increase the expression of certain genes, instead of the more traditional technique of actively cutting or editing DNA. The method was tested in mice by targeting two genes associated with hunger, with the animals reducing their food intake and not becoming obese.

The new gene modification technique, developed at UCSF, is called CRISPR-mediated activation (CRISPRa). The method utilizes CRISPR's ability to target a specific DNA sequence but instead of cutting out a gene, or editing in a new one, it can more simply increase the expression of its target gene. The CRISPRa method reportedly results in less potential off-target effects as it isn't causing any permanent change to a genome.

Our human genome holds two copies of every gene. A large variety of human diseases are the result of mutations in one copy of the gene in a pair. To test the efficacy of the CRISPRa method, the researchers focused on two genes known to regulate satiety and hunger, SIM1 and MC4R. Individuals suffering from severe obesity often have mutations in one of those genes, resulting in unregulated appetite and overeating.

The CRISPRa method was deployed in mice that were genetically modified to only have one working copy of either the SIM1 or the MC4R gene. The results were undeniably impressive, with the animals receiving the CRISPRa boost ultimately expressing amounts of both genes comparable to animals with two working copies of the genes.