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Rationally Designed Synthetic Vectors for Gene Delivery 合理设计基因传递合成载体
Pub Date : 2007-07-12 DOI: 10.2174/1874126600701010007
Gururaj A. Rao, Preeti Yadava, J. Hughes
Vector development is one of the most important challenges facing the successful use of genes for treatment of diseases. Although chemically produced vectors offer distinct advantages over biological systems such as viruses, there are still some hurdles that have to be overcome before synthetic gene delivery vectors can be successfully implemented. This brief review discusses the biological barriers that limit current delivery strategies and reviews currently employed strategies for plasmid delivery. Nanoparticle-based gene delivery is reviewed along with methods for their characteriza- tion, physiochemical properties and toxicity. Finally a prospectus is provided for future development of an ideal synthetic gene delivery vector. GENE THERAPY Gene therapy involves the use of exogenous DNA as the therapeutic agent. Originally it was targeted towards treat- ment of inheritable single-gene disorders caused due to an absent or defective gene. However, applications of gene therapy have expanded to include treatment of acquired and infectious diseases and exogenously administered genes now are used in a wide variety of applications including immu- nomodulation, genetic vaccination and genetic pharmacol- ogy (1-6).
病媒发展是成功利用基因治疗疾病所面临的最重要挑战之一。尽管化学产生的载体比病毒等生物系统具有明显的优势,但在成功实施合成基因传递载体之前,仍有一些障碍必须克服。这篇简短的综述讨论了限制当前递送策略的生物障碍,并综述了目前采用的质粒递送策略。综述了基于纳米颗粒的基因传递及其表征、理化性质和毒性的方法。最后对未来理想的合成基因传递载体的发展进行了展望。基因治疗包括使用外源DNA作为治疗剂。最初,它是针对治疗遗传性的单基因疾病引起的缺失或缺陷的基因。然而,基因治疗的应用已经扩大到包括治疗获得性疾病和传染病,外源给药基因现在被广泛用于各种应用,包括免疫调节、遗传疫苗接种和遗传药理学(1-6)。
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引用次数: 9
Effect of Insulin and Losartan on Modulation of Insulin-Like Growth Factor 1 Receptor at Heart Level in Diabetic Rats 胰岛素和氯沙坦对糖尿病大鼠心脏水平胰岛素样生长因子1受体调节的影响
Pub Date : 2007-07-12 DOI: 10.2174/1874126600701010001
A. Bikhazi, Wael M Maharsy, Lina N. Kadi, N. Issa, Ghinwa M. Barakat, N. Nuwayri-Salti, G. Karam, O. Batal, K. Bitar
This study investigates insulin-like growth factor-1 receptor (IGF-1R) modulation in hearts of streptozotocin- induced diabetic rats treated with insulin/angiotensin-II receptor subtype-1 blocker (AR1B), losartan. Male rats were di- vided into: normal (N), losartan-treated normal (NL), diabetic (D), insulin-treated diabetic (DI), losartan-treated diabetic (DL), and insulin/losartan co-treated diabetic (DIL) groups. Thirty days post-treatment, rats underwent heart perfusion us- ing (I 125 )-labeled IGF-1 to assess receptor-binding affinity on coronary endothelial cells (CE) and cardiomyocytes (CM). This revealed an increase in binding affinity of IGF-1 to its receptor on CE in all groups compared to N. On CM, binding affinity increased in D, DI, and DL compared to N, but was almost normalized in DIL. Western blot analyses and immu- nohistochemistry done on heart tissues showed decrease in IGF-1R density in DIL versus remaining groups. These results demonstrate a complex interaction between insulin, angiotensin-II, and IGF-1, and mass blockade of myocardial remodel- ing by AR1B treatment in diabetic state.
本研究探讨胰岛素/血管紧张素- ii受体亚型-1阻滞剂(AR1B)氯沙坦治疗链脲佐菌素诱导的糖尿病大鼠心脏中胰岛素样生长因子-1受体(IGF-1R)的调节。雄性大鼠分为:正常(N)组、氯沙坦治疗的正常(NL)组、糖尿病(D)组、胰岛素治疗的糖尿病(di)组、氯沙坦治疗的糖尿病(DL)组和胰岛素/氯沙坦共治疗的糖尿病(DIL)组。治疗后30天,大鼠进行心脏灌注(i125)标记的IGF-1,以评估受体对冠状动脉内皮细胞(CE)和心肌细胞(CM)的结合亲和力。这表明IGF-1与受体在CE上的结合亲和力在所有组中都比N增加。在CM上,与N相比,D、DI和DL的结合亲和力增加,但在DIL中几乎归一化。Western blot分析和对心脏组织进行的免疫组织化学分析显示,与其他组相比,DIL组IGF-1R密度降低。这些结果表明胰岛素、血管紧张素- ii和IGF-1之间存在复杂的相互作用,并通过AR1B治疗对糖尿病状态下心肌重构的大规模阻断。
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引用次数: 1
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The Open Drug Delivery Journal
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