Scientists recently made an exciting discovery suggesting that CRISPR therapies can prevent obesity without cutting or editing a DNA. The study- conducted by the UC San Francisco scientists, describes how CRISPR can be used to increase the activity of certain genes and prevent obesity.
Scientists dubbed this technique as CRISPR-mediated activation (CRISPRa). It uses 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.
Scientists tested this technique on mice by targeting two genes associated with hunger, with the animals reducing their food intake and not becoming obese. Scientists targeted two genes known to regulate satiety and hunger, SIM1 and MC4R.
The outcomes were evidently great, with the animals getting the CRISPRa help boost ultimately expressing of the two genes practically identical to animals with two working copies of the genes.
Lead author on the new study, Navneet Matharu said, “The results were dramatic. Mice that were missing one copy of the Sim1 gene received the CRISPRa injections at four weeks of age and maintained a healthy body weight like normal mice.”
“Mice that didn’t receive CRISPRa injections couldn’t stop eating. They started gaining weight at six weeks of age, and by the time they were 10-weeks old, they were severely obese on a regular diet.”
CRISPRa-treated mice were 30 to 40 percent lighter than their untreated counterparts. The effects were also long-lasting. The researchers monitored the mice for 10 months – a significant fraction of a mouse’s normal lifespan – and found that those that received a single CRISPRa treatment maintained a healthy weight for the duration of their monitoring.
According to scientists, CRISPRa has a number of advantages over the standard version of the gene-editing technology. It could be preferable to conventional CRISPR. It solves many of the problems associated with making permanent modifications to the genome, and it has the potential to treat a variety of genetic diseases for which gene editing isn’t an option.
However, off-target effects associated with CRISPRa are less likely to be damaging because no permanent changes are made. In fact, the new study shows that using CRISPRa to target promoters and enhancers – noncoding DNA sequences that control when and where a gene is turned on – seems to prevent off-target effects while confining the desired effects to specific tissues of interest.
CRISPRa can also be used to:
- Treat other kinds of a genetic disease such as microdeletions.
- Compensate for the deletion by increasing the activity of several genes on the unaffected copy of the chromosome
Nadav Ahituv, PhD, professor of bioengineering and therapeutic sciences said, “Though this particular study focused on obesity, we believe our system could be applied to any situation in which having only one functional copy of a gene leads to disease. Our method demonstrates tremendous therapeutic potential for numerous diseases, and we show that we can achieve these benefits without making any edits to the genome.”
The paper is published Dec. 13, 2018, in the journal Science.