Zheng Mumin, Zhang Shuwen, Wang Yunna, Xie Ning, Wang Xiaodan, Lv Jiaping, Pang Xiaoyang, Li Xu
Key Laboratory of Agro-Products Quality and Safety Control in Storage and Transport Process, Ministry of Agriculture and Rural Affairs, Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
Foods. 2025 May 17;14(10):1785. doi: 10.3390/foods14101785.
Type 2 diabetes is one of the main causes of cardiovascular diseases, kidney diseases, and visual impairments, posing a global healthcare challenge. The current treatment of this disease, involving glucagon-like peptide-1 (GLP-1), is faced with problems such as frequent injections and plasmid instability. In this study, we used the native clustered regularly interspaced short palindromic repeats-CRISPR-associated protein 9 (CRISPR-Cas9) system of to develop a novel, genetically stable, and orally administrable strain expressing human GLP-1. Integration and subsequent expression of glp-1 gene were confirmed by genomic sequencing, qPCR, and Nano LC-MS. The engineered strain demonstrated stable genomic integration and sustained high-level expression of GLP-1 over multiple generations. This innovative approach provides a promising strategy for the oral delivery of therapeutic peptides, potentially enhancing patient compliance and improving the treatment of diabetes and other chronic diseases requiring peptide-based therapies.
2型糖尿病是心血管疾病、肾脏疾病和视力障碍的主要病因之一，给全球医疗保健带来挑战。目前针对该疾病的治疗涉及胰高血糖素样肽-1（GLP-1），但面临频繁注射和质粒不稳定等问题。在本研究中，我们利用天然的成簇规律间隔短回文重复序列-CRISPR相关蛋白9（CRISPR-Cas9）系统开发了一种新型的、基因稳定且可口服的表达人GLP-1的菌株。通过基因组测序、定量聚合酶链反应（qPCR）和纳升液相色谱-质谱联用（Nano LC-MS）证实了glp-1基因的整合及随后的表达。该工程菌株在多代中表现出稳定的基因组整合和GLP-1的持续高水平表达。这种创新方法为治疗性肽的口服递送提供了一种有前景的策略，可能提高患者的依从性，并改善糖尿病和其他需要基于肽疗法的慢性病的治疗。
