Recent progress in polymer-based gene delivery vectors

The gene delivery system is one of the three components of a gene medicine, which is the bottle neck of current gene therapy. Nonviral vectors offer advantages over the viral system of safety, ease of manufacturing, etc. As important nonviral vectors, polymer gene delivery systems have gained increasing attention and have begun to show increasing promising. In this review, the fundamental and recent progress of polymer-based gene delivery vectors is reviewed.     

使用病毒载体的罕见病基因疗法临床进展

 很大一部分的罕见病由遗传因素决定,难以用普通的小分子或大分子药物治愈,而基因治疗有望从根本上修正人体功能的缺失或异常,给罕见病患者带来改善生活质量的希望。目前许多基因疗法的临床试验正在开展,病毒载体是常用的基因递送方法,本文讨论了用于临床基因递送的多种病毒载体,包括腺相关病毒、逆转录病毒和慢病毒,重点列举了这些病毒在罕见病临床试验中的研究、应用和进展,评价了这些病毒的优缺点,并简述了基因疗法的研究方向及应用前景。     

Adenovirus-mediated<Emphasis Type="Italic">CTLA4-FasL</Emphasis> gene transfer prevents autoimmune diabetes in mice induced by multiple low doses of streptozotocin

Type 1 diabetes is the result of a selective destruction of insulin-producing β cells in pancreatic islets by autoreactive T cells. Depletion of autoreactive T cell through apoptosis may be a potential strategy for the prevention of autoimmune diabetes. Simultaneous stimulation of Fas-mediated pathway and blockade of costimulation by a CTLA4-FasL fusion protein has been reported to lead to substantial inhibition of mixed lymphocyte reaction and enhanced in vitro apoptosis of peripheral lymphocytes. To test the feasibility of CTLA4-FasL-based gene therapy to prevent autoimmune diabetes, we developed recombinant adenovirus containing human CTLA4-FasL gene (AdCTLA4-FasL). A single injection of 2×10~8 plaque forming units (PFU) of AdCTLA4-FasL via tail vein dramatically reduced the incidence of autoimmune diabetes in mice induced by multiple low doses of streptozotocin. AdCTLA4-FasL administration maintained islet insulin content, significantly increased apoptosis of pancreatic lymphocytes, quantitatively     

Research advances in gene therapy for Parkinson's disease

During the long period of time when people have been seeking for an effective therapeutic method for PD, the gene therapy has shown greater and greater advantages over other methods. It can be performed mainly in two ways: ex vivo and in vivo. With the former, TH gene as well as some neurotrophic factor genes (such as GDNF, BNDF genes) can be invited to some cell lines or primary cells thus forming engineered cells and then implanting them into brain. While with the latter, viral vectors including HSV-1, Ad, AAV that can be utilized to construct recombinant viruses, or non-virus vectors can be used to delived DNA into brain directly. The present review summarizes the recent research advances in the gene therapy for PD, and it is reasonable for us to predict a notable progress in prevention and treatment for PD in the next decade.     

Therapeutic angiogenesis induced by human hepatocyte growth factor gene in hindlimb ischemia of dogs

A preclinical study of treating peripheral srtery occlusive disease(PAD) was performed by using a hepatocyte growth factor(HGF) gene-expressing vector,plasmid pUDKH,in a dog model with complete ischemia of one hindlimb.After ligation of femoral artery of one hindlimb,pUDKH was transferred directly into the ischemic limb muscles.The angiogenic activity of the plasmid pUDKH was evaluated.On D 30 after injecting once of pUDKH at differ-ent doses into local muscles immediately after operation,the degree of augmentation of collateral vessel formation was significantly greater than that treated by blank vector.In addition,the blood flow rate of femoral artery in dogs treated with pUDKH was recovered on D90,while the folw rate was only 1/5 tp 1/3 in control dogs.The pulse amplitude of pUDKH-treated dogs was recovered on D90,but it was hardly detectable in most of the control dogs.The side effects of intramuscular transfection of pUDKH were also investi-gated,and no significant positive change was found.It is suggested that angiogenesis induced by HGF gene has the potential for clincal use in the treatment of peripheral arte-rial diseases.     

Therapeutic angiogenesis induced by human hepatocyte growth factor (HGF) gene in rat myocardial ischemia models

Coronary arteriosclerotic cardiopathy is also named myocardial ischemia, which severely threatens humanhealth. Following the economic development and change of life style in China, population blood pressure, weight index and serum cholesterol level all rise. This prophesies incidence rate of coronary arteriosclerotic cardiopathy and stroke will increase year by year. Angioplasty and surgical bypass, the primary interventional therapies for these in-dividuals, are temporally limited by the prob…     

Adeno-associated virus-mediated integration and expression of human P-globin gene with the core fragment of locus control region in erythroid cells

To improve the integration stability and expression of the transferred human p-globin gene, the two recombinant adeno-associated virus (AAV) vectors containing the human [3-globin gene with a single or multiple DNase I hypersensitive site (HS) core fragment of the LCR were constructed. These recombinants were respectively introduced into MEL cells via AAV-mediated gene transfer to investigate their integration and expression. The results suggested that following AAV vector-mediated gene transfer, the human [3-globin gene with the multiple HS core fragment of the LCR could steadily integrate into MEL cells and confer an expression level comparable with endogenous mouse a-globin gene.