In conventional insulin gene therapy, exogenous insulin gene is usually transferred by caudal vein injection, portal vein injection, intraperitoneal injection, or intramuscular injection. They are invasive methods and can result in infections or death. The target cells in these methods mainly focus on hepatic cell and skeletal muscle cell. But hepatic cell and skeletal muscle cell are not endocrine cells. These cells usually need to be genetically modified in responsibility to glucose and processing from proinsulin to insulin. One factor critical to successful gene therapy is the development of efficient delivery systems. Although viral vectors can introduce exogenous genes into cells precisely and effectively, it can easily cause immune reactions because of the existence of antivirotic immune system. At present, there is no report for transfection of human insulin gene to gastrointestinal tracts. And there is no report for application of chitosan as a vector in the gene therapy for type 1 diabetes mellitus.
A research article to be published on 14 July 2008, in the World Journal of Gastroenterology addresses this question. The research team led by Prof. Yan-Cheng form Zhongnan Hospital of Wuhan University. Some gastrointestinal endocrine cells are the potential and ideal target cell in the gene therapy of diabetes. Human insulin gene transferred to diabetic rats by gastrointestinal tracts is very safe and without any wound, and can avoid infections effectively. A perfect vector should also be biocompatible, efficient, and modular so that it is tunable to various applications in both research and clinical settings. Chitosan is an ideal non-viral vector and has drawn wide attention. Taking into consideration these facts, the study attempted to transfer exogenous human insulin gene by gastrointestinal tracts.
A plasmid pCMV.Ins expressing human insulin gene was constructed. It was wrapped with chitosan nanoparticles, a non-viral vector, and transfected to diabetic rats through lavage and coloclysis respectively. Fasting blood glucose and plasma insulin were measured. RT-PCR analysis and western blot analysis were performed to confirm the expression of human insulin gene. The blood glucose of diabetic rats decreased significantly, and the plasma insulin increased correspondingly. The human insulin gene wrapped with chitosan nanoparticles can be transfected successfully and expressed efficiently in the gastrointestinal tracts of diabetes rats.
These findings demonstrate that chitosan is a promising non-viral vector. Endocrine cells in gastrointestinal may be the potential target cells in gene therapy of type 1 diabetes mellitus. The most superiority of this study is its safety and without any wound. If it can be applied in clinic, it will be accepted by patients willingly. Chitosan is an ideal non-viral vector and can be widely used in gene transfer. The study gives new ideas and technologies to endocrine cells in gastrointestinal tracts and gene transfer.
Reference: Niu L, Xu YC, Dai Z, Tang HQ. Gene therapy for type 1 diabetes mellitus in rats by gastrointestinal administration of chitosan nanoparticles containing human insulin gene. World J
Gastroenterol 2008; 14(26): 4209-4215:
Correspondence to: Professor Yan-Cheng Xu, Department of Endocrinology, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan 430071, Hubei Province, China. firstname.lastname@example.org
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World Journal of Gastroenterology (WJG), a leading international journal in gastroenterology and hepatology, has established a reputation for publishing first class research on esophageal cancer, gastric cancer, liver cancer, viral hepatitis, colorectal cancer, and H pylori infection and provides a forum for both clinicians and scientists. WJG has been indexed and abstracted in Current Contents/Clinical Medicine, Science Citation Index Expanded (also known as SciSearch) and Journal Citation Reports/Science Edition, Index Medicus, MEDLINE and PubMed, Chemical Abstracts, EMBASE/Excerpta Medica, Abstracts Journals, Nature Clinical Practice Gastroenterology and Hepatology, CAB Abstracts and Global Health. ISI JCR 2003-2000 IF: 3.318, 2.532, 1.445 and 0.993. WJG is a weekly journal published by WJG Press. The publication dates are the 7th, 14th, 21st, and 28th day of every month. WJG is supported by The National Natural Science Foundation of China, No. 30224801 and No. 30424812, and was founded with the name of China National Journal of New Gastroenterology on October 1, 1995, and renamed WJG on January 25, 1998.
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