This year, the Squirrel-CHN team focused on addressing the significant health issues of overweight and obesity, contributing 6 basic parts and 2 composite parts as part of their project. They explored an innovative gene therapy-based solution aimed at overcoming the inconvenience of injectable medications. By designing genetically engineered bacteria that can stably secrete GLP-1 in the intestines, this project provides a new oral treatment option for overweight patients, eliminating the discomfort and psychological burden associated with injections.

BBa_K5083000: GLP-1 coding sequence, responsible for producing GLP-1 hormone, mimicking the effects of medications used to treat obesity and overweight.

BBa_K5083001: PelB-GLP-1 fusion protein, designed to enhance secretion and optimize GLP-1 delivery in the intestines.

BBa_K5083002: Bimagrumab coding sequence, an antibody that helps reduce fat and increase muscle mass, contributing to obesity treatment.

BBa_K5083003: DPP-4 inhibitor, which prolongs the activity of GLP-1 by inhibiting the DPP-4 enzyme, enhancing the therapeutic effect.

BBa_K5083004: T4 holin, used to design a suicide switch system, controlling the lysis of engineered bacteria to ensure treatment safety.

BBa_K5083005: T4 lysozyme, also used in the bacterial lysis system to further control the survival of the engineered bacteria.

BBa_K5083098: pBAD-T4 holin-T4 Lysozyme, a lysis system regulated by the pBAD promoter, ensuring that bacteria lyse under specific conditions, controlling the survival time of the engineered bacteria.

BBa_K5083099: pCspA-T4 holin-T4 Lysozyme, a lysis system expressed under low-temperature conditions, making it more suitable for the varying temperatures of the intestinal environment.

The work of the Squirrel-CHN team not only lays the groundwork for oral GLP-1 producing engineered bacteria, advancing new approaches to obesity treatment, but also introduces significant innovations in genetic regulation and safety system design. With their optimization of PelB-GLP-1 secretion and the development of the T4 lysis system as a bacterial suicide switch, their project provides valuable experience for future teams in designing therapeutic engineered bacteria, safety-regulated suicide switches, and integrated multi-level control elements. This will open new avenues for future iGEM projects in areas such as chronic disease treatment and biosafety control.

This research not only offers a more convenient treatment option for patients suffering from obesity and overweight but also holds broad potential applications in treating other chronic diseases. It also sparks greater interest in the application of genetic engineering in medicine.