Researchers at the University of Chicago modified the glucagon peptide (GLP 1) receptor gene by using CRISPR technology. GLP 1 receptor gene can stimulate pancreas to secrete insulin, remove excessive blood sugar and prevent diabetic complications. At the same time, GLP 1 can also delay gastric emptying and reduce appetite.
The researchers extended the half-life of GLP 1 receptor gene in blood in a specific way, and integrated the modified gene into an antibody fragment to make it run in blood for a longer time. In addition, they added an inducible promoter, which enabled them to turn on genes as needed and produce more GLP 1. Then, the researchers inserted the gene into skin cells for culture and let them grow. When the cultured cells are exposed to the gas/liquid interface in the laboratory, stratification will occur, resulting in multilayer "skin-like organs". When the transgenic skin cultured in the laboratory was transplanted into mice with intact immune system, the researchers found no obvious rejection.
The study also found that when eating food containing a small amount of doxycycline, mice will release GLP 1 into the blood at a dose-dependent level, thus increasing the supply of insulin in the blood in time and lowering the blood sugar level.
On the other hand, when normal mice and transgenic mice are fed with high-fat food, they will gain weight quickly and become obese. Adding different levels of doxycycline while feeding high-fat food can induce the release of GLP 1, and normal mice will become obese; However, transgenic mice gained less weight. When the researchers transplanted transgenic human cells into mice with limited immune systems, they found the same effect. This shows that skin gene therapy induced by GLP 1 can be used to prevent and treat obesity and other diseases caused by diet.
It is said that this method of combining accurate gene editing in vitro with effective application of engineered cells in vivo will provide a long-term and safe choice for the treatment of many human diseases, such as replacing the missing protein for patients with genetic defects (hemophilia) or acting as a metabolic bank to eliminate toxins in vivo.