Pub Date : 2007-07-12DOI: 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).
{"title":"Rationally Designed Synthetic Vectors for Gene Delivery","authors":"Gururaj A. Rao, Preeti Yadava, J. Hughes","doi":"10.2174/1874126600701010007","DOIUrl":"https://doi.org/10.2174/1874126600701010007","url":null,"abstract":"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).","PeriodicalId":421840,"journal":{"name":"The Open Drug Delivery Journal","volume":"51 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2007-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133699142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2007-07-12DOI: 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.
{"title":"Effect of Insulin and Losartan on Modulation of Insulin-Like Growth Factor 1 Receptor at Heart Level in Diabetic Rats","authors":"A. Bikhazi, Wael M Maharsy, Lina N. Kadi, N. Issa, Ghinwa M. Barakat, N. Nuwayri-Salti, G. Karam, O. Batal, K. Bitar","doi":"10.2174/1874126600701010001","DOIUrl":"https://doi.org/10.2174/1874126600701010001","url":null,"abstract":"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.","PeriodicalId":421840,"journal":{"name":"The Open Drug Delivery Journal","volume":"101 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2007-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123202419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}