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flower8359银虫 (小有名气)
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第一段 INTRODUCTION Interest in gene therapy has been renewed because of its exciting results in clinical trials. In recent years, gene therapy clinical trials for cancer are moving rapidly from phase I to III, and the first anti-cancer gene therapy drug has been licensed in China 1. In the protocol of clinical gene therapy, the therapeutic gene was designed to introduce into patents’ cells to cure the acquired or inherited disease in genetic level by adding, correcting, or replacing gene 2. Since gene is prone to be rapidly degraded by nuclease and exhibit poor cellular uptake when delivered in aqueous solutions, the development of effective delivery platforms that prevent their degradation and facilitate cellular uptake is a key issue 3. Viral vectors are mostly used as gene carriers in current clinical and preclinical trials. Besides the relatively high gene expression of viral gene vectors, there are concerns over endogenous recombination, oncogenic effects and immunological reactions leading to potentially serious complications 4,5, which have resulted in parallel efforts to develop non-viral alternatives due to the improved safety profile, easy to preparation and manipulation compared with viral vectors 6. 第二段 As non-viral gene carriers, cationic polymers, such as poly-L-lysine (PLL), polyethylenimine (PEI), and poly (amido amine) dendrimer have attracted an increasing interest, which are contributed to their positive charge nature at physiological pH 7-9. Gene materials can be condensed into nanoparticles, and protected from enzymatic degradation via complexes formed between gene and polycation, and facilitating the cell uptake and endolysosomal escape 10. 第三段 Of all the cationic polymers, PEI is known as the one of the most effective gene carriers invitro because of its “proton sponge effect” in endolysosome 11. Previous reports showed that high transfection efficiency of PEI, along with its cytotoxicity, greatly depended on its molecular weight 12,13. It is generally believed that PEI with a molecular weight higher than 25 KDa displays high transfection efficiency and cytotoxicity due to its non-degradability and high charge density, while PEI with a molecular weight less than 1.8 KDa shows low transfection but is less toxic 14. It was also well known that cationic polymer, including PEI-mediated gene transfection in vitro was most efficient at an excess of cationic polymer leading to positively charged polyplexes which bind to anionic cell surfaces, facilitateing the cell uptake. Unfortunately, positively charged polyplexes interact unnecessarily with serum components along with precipitation and reduction of the blood circulation time 15. Additionally, the polyplexes showed a tendency to aggregate due to the decreased water solubility induced by charge neutralization through the electrostatic interaction between polycationic vectors andpolyanionic DNA 14. To overcome the inherent barriers of polyplexes, such as solubility,cytotoxicity, and half-life in blood stream, various nonionic water-soluble polymers, such as poly(N-vinyl pyrrolidone) (PVP), poly(ethylene glycol) (PEG), poly[N-(2-hydroxypropyl)-methacrylamide] (PHPMA) have been grafted onto PEI 15-18. |
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wshbinzhang
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9楼2009-02-16 22:11:25
flower8359
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wshbinzhang
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★ ★ ★
flower8359(金币+1):谢谢参与
flower8359(金币+2,VIP+0):谢谢 2-18 07:54
flower8359(金币+1):谢谢参与
flower8359(金币+2,VIP+0):谢谢 2-18 07:54
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第一段 In the protocol of clinical gene therapy, the therapeutic gene was designed to introduce into patents’ cells to cure the acquired or inherited disease in genetic level by adding, correcting, or replacing gene 2. was 应该为is保持前后时态一致 |
3楼2009-02-16 21:59:19
wshbinzhang
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4楼2009-02-16 22:00:57