Gene Amplification Controls Obesity in Mice

Researchers used CRISPR activation rather than editing to increase the role of the satiety gene.

CRISPR (short for clustered regularly interspaced short palindromic repeats) technology is typically used to edit genomic information by removing undesirable sequences –– notably mutations –– from the genetic code. Researchers at the University of California, San Francisco (UCSF) have taken a different approach, modifying the technology so that it amplifies the activity of good genes. They call the new method, which targets noncoding DNA sequences that turn genes on and off, CRISPRa (for activation).

The technology was recently tested as a means of controlling obesity. Severe obesity has been linked to mutations in the single-minded 1 (SIM1) and melanocortin 4 receptor (MC4R) genes, which regulate food intake by signaling the feeling of being full. Mutations in these genes result in a feeling of constant hunger.

The UCSF researchers used CRISPRa to boost the activity of working copies of the satiety genes in mice with only one working copy of either SIM1 or MC4R. Mice that received an injection of the CRISPRa treatment weighed up to 40% less than those that did not receive an injection.

Because CRISPRa does not permanently alter the genetic code, the researchers believe it has an advantage over gene editing, which some fear could cause dangerous off-target effects. The scientists are looking at the potential application of CRISPRa to other diseases, such as those caused by missing copies of genes or by microdeletions, the loss of large segments of chromosomes.

David Alvaro, Ph.D.

David is Scientific Editor in Chief of the Pharma’s Almanac content enterprise, responsible for directing and generating industry, scientific and research-based content, including client-owned strategic content, in addition to serving as Scientific Research Director for That's Nice. Before joining That’s Nice, David served as a scientific editor for the multidisciplinary scientific journal Annals of the New York Academy of Sciences. He received a B.A. in Biology from New York University in 1999 and a Ph.D. in Genetics and Development from Columbia University in 2008.