Biointegrated sensors can address various challenges in medicine by transmitting a wide variety of biological signals. A tempting possibility that has not been explored before is whether we can take advantage of genome editing technology to transform a small portion of endogenous tissue into an intrinsic and long-lasting sensor of physiological signals. The human skin and epidermal stem cells have several unique advantages, making them particularly suitable for genetic engineering and applications in vivo. In this report, we took advantage of a novel platform for manipulation and transplantation of epidermal stem cells, and presented the key evidence that genome-edited skin stem cells can be exploited for continuous monitoring of blood glucose level in vivo. Additionally, by advanced design of genome editing, we developed an autologous skin graft that can sense glucose level and deliver therapeutic proteins for diabetes treatment. Our results revealed the clinical potential for skin somatic gene therapy.
To make their biological invention, Wu and team first collected from mice some of the stem cells whose job it is to make new skin. Next, they used the gene-editing technique CRISPR to create their built-in glucose detector. That involved adding a gene from E. coli bacteria whose product is a protein that sticks to sugar molecules.
Next, they added DNA that produces two fluorescent molecules. That way, when the E. coli protein sticks to sugar and changes shape, it moves the fluorescent molecules closer or further apart—generating a signal that Wu’s team could see using a microscope.
All that was done in a lab dish—so next the team tested whether the glucose-sensing cells could be incorporated into a mouse’s body by grafting the engineered skin patches onto their backs. When mice who were left hungry were suddenly given a big dose of sugar, Wu says, the cells reacted within 30 seconds. Measuring glucose this way was just as accurate as a blood test, which they also tried.