A new weighted study shows that CRISPR therapies can cut fat without breaking DNA. In a paper published December 13, 2018, in the magazine ScienceUC San Francisco researchers describe how a revised version of CRISPR was used to raise the activity of some genes and to prevent severe obesity in mice with genetic mutations that preceded them to gain extreme weight. Significantly, researchers managed to control permanent pressure without editing the genome.
Single-Single Copy Discharges In Many Human Diseases
Although the human genome contains two copies of each gene in an individual, one in each parent, scientists know at least 660 genes where mutation in one copy can only lead to diseases, some of which are destructive. Such a condition is serious obesity, which the authors of the new study used as a model to develop a new therapeutic approach to treating these disorders.
Mutations in one copy of SIM1 or MC4R – two genres that are critical for starving and starving regulation – are the most common mutations in obese individuals. When both copies of these genes operate, people in general can control their food. But mutations can make one copy that is not functional, enforcing the body to rely exclusively on a working-only copy, which alone, is significant in wording, leaving individuals experiencing incredible disorders. As a result, they can not control their food intake and are overweight as obese. But recent developments in CRISPR technology can offer a solution.
"We thought, if we could increase the dose of the current functional copy of the gene, we could stop many human diseases in individuals who are passionate about these mutations," said Nadav Ahituv, PhD, teacher bio-production and therapeutic sciences and senior study author. "We were able to achieve this by using the new CRISPR technology developed here at UCSF."
CRISPRa is Active Mouth Taste-Prevention
The technology in question is CRISPRa (for operation). After developing at UCSF at the laboratory Jonathan Weissman, PhD, a cellular and molecular pharmacist teacher, CRISPRa differs from a conventional CRISPR as it does not make genome cuts. It holds a CRISPR instruction system, which can be programmed to homes on a specific DNA sequence, but it replaces the molecule scissors with a volume control blast. When CRISPRa finds its target, it broadens the activity of that gene. No adjustments are made.
Recognizing its potential, researchers created CRISPRa systems that target sequences that regulate SIM1 or MC4R activity. They use a viral supplying system to introduce these CRISPRa into the brain controller's in mice that were genetically engineered to obtain only one functional copy of the gene.
Mice received by CRISPRa produced more SIM1 or MC4R than those that did not. Additionally, the amounts similar to the mice that usually have two copies that work from these genera produce them. Most importantly, the increasing dose was enough to prevent the mice becoming obese.
"The results were dramatic.The missing mice had a single copy of the SIM1 gene receiving CRISPRa injections at four weeks and keeping healthy body weight like normal mice. Mice that did not accept CRISPRa injections stopped eating. Weight gain began for six weeks, and by 10 weeks of age, they were seriously obese on a regular diet "said Navneet Matharu, PhD, researcher at Ahituv's laboratory and lead author of the new study .
CRISPRa-treated mice were 30 to 40 percent lighter than their untreated peers. The effects were also permanent. The researchers monitored the rats for ten months – a significant fraction of the normal age of the mouse – and those who had a single CRISPRa treatment were found to keep healthy weight during their monitoring.
"These results show that CRISPRa can be used upstream genes in diseases that are a result of a missing copy, providing a possible recovery for specific types of obesity as well as hundreds of other diseases, "said Matharu.
CRISPRa Can Overcome Genes Editing Limitations
Researchers believe that they may have achieved similar results using CRISPR to mean genomes and these mice, but they argue that CRISPRa has many advantages over the standard version of gene editing technology.
"For therapeutic purposes, CRISPRa may be better than a 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 that genes editing is not an option, "said Christian Vaisse, MD, PhD, Chairman of Vera M. Long Endowed in Diabetes Research at UCSF and co-author of the study.
Although CRISPR targets specific DNA sequences, impacts have been observed off target. With a conventional CRISPR, this can lead to unintentional but permanent changes to the genome with potentially damaging consequences. However, off-target effects associated with CRISPRa are less likely to be detrimental as no permanent changes are made. In fact, the new study shows that using CRISPRa to target promoters and enrichers – there are non-corrected DNA sequences that control when and when a gene is turned on – it's it seems to prevent off-target effects while restricting the desired effects to specific tissues of interest.
The researchers also note that CRISPRa could be used to treat other types of genetic disease. There are diseases that are derived from the "microdeletions" known as remarkable – there is a term that refers to the loss of large chromosome segments that involve millions of nucleotides and multiple genes – It's too big for a conventional CRISPR to repair. In such cases, CRISPRa could be used to compensate for the removal by increasing the activity of several genera on the disused copy of the chromosome. And in cases where a gene has lost completely, CRISPRa could operate another gene with a similar function to compensate for the missing gene, says the researchers.
"Although this specific study focuses on obesity, we believe that our system could be used to any situation where one functional copy of a gene leads to a disease," said Ahituv. "Our approach shows tremendous therapeutic potential for a number of diseases, and we show that we can achieve these benefits without making any changes to the genome."