The purposes of writing this review article is the significant role of diabetes in our life, the increasing risk of the onset of diabetes and hoping to treat this important multifactorial disease. the effort for treating diabetes through transplanting pancreatic islet hadn’t been successful. but gene therapy is a useful technique to treat t1dm. gene therapy for t1dm consists of replacing insulin gene in a host as a treatment way and suppressing autoreactive t-cells as a prevention way. as the achievement of gene and cell therapy in t2dm are less evident, in this article, different methods of gene therapy for t1dm was discussed. some gene therapy techniques for t1dm are ectopic gene expression, systemic gene expression, express anti-apoptotic molecules, using core peptide, using immunoregulatory cytokines for inhibiting nk and t-cells activities, preventing of interactions between apc and t-cells and manipulating stem cells for entering hla-g gene into them. ectopic gene expression is a widely used technique. good alternatives to β-cells for manipulation into insulin producing cells, include stem cells, hepatocytes, epithelial cells and etc.
Methods
One step in gene therapy is transferring genes into cells. gene transfer techniques that were used in researches for gene therapy are devided into two groups; non-viral vectors and viral vectors. some non-viral vectors are lipofectin, direct microinjection, electroporation and biolistics. viral vectors are retrovirus, adenovirus and lentivirus. the vectors that were used for ectopic gene expression in epithelial cells were retrovirus and lentivirus with cmv promoter or gip promoter; in hepatocytes were adenovirus, lentivirus and adeno-associated vector; in stem cells was retrovirus with cmv promoter. in these researches that i’ve studied, mice and rats were used as an animal models. the results were analyzed by eliza and flow cytometry. epidermal keratinocytes were used as an epithelial cell and murin mesenchymal stem cells were used as a stem cell for ectopic gene expression. dendritic cells were used for expression of core peptide.
Results
All of those techniques have been greatly successful. manipulating stem cells for entering hla-g gene into them, constantly leaded to producing β-cells. ectopic gene expression in hepatocytes with lentivirus has leaded immediate reduction of bgls.
Conclusion
All of those techniques have advantages and disadvantages: non-β-cells could be modified to secrete insulin but they don’t have the proteases required for producing mature insulin; keratinocytes and hepatocytes are good candidates for ectopic gene expression of insulin; redirection of hepatocytes to islet life function is a possible treatment for t1dm; use stem cells in a correct way, can overcome the autoimmune response; the main disadvantage of retroviral transduction is that they are only able to transduce cells that are currently dividing. they maybe also randomly integrate.
