Toward development of artificial viruses for gene therapy: A comparative evaluation of viral and non-viral transfection
Toward development of artificial viruses for gene therapy: A comparative evaluation of viral and non-viral transfection
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DOI：
10.1021/bp070319o
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发表时间：
2008-07-01
影响因子：
2.9
通讯作者：
Douglas, Kimberly L.
中科院分区：
文献类型：
--
作者：
Douglas, Kimberly L.
与基因疗法的安全性和有效性相关的问题已经抑制了人们对该领域的热情，尽管它仍然是治疗多种疾病的一种有前途的方法。尽管使用病毒载体可实现高转染效率，但制造困难。安全问题以及与靶向和质粒大小相关的限制促使人们对非病毒载体的开发进行了大量研究。非病毒载体表现出低毒性、低免疫原性且易于制造。然而，它们尚未达到病毒所显示的转染效率。无法解释或预测转染效率的部分原因是。对基因传递所涉及的细胞内过程了解不足。人们越来越多地进行研究来探索克服载体介导转染的主要障碍的过程：(1) 内化，(2) 细胞内运输，(3) 逃逸至细胞质，(4) 核易位，以及 (5) 基因转录/表达。本文回顾并比较了成功的病毒和非病毒转染所涉及的途径和技术。此外，本综述提供的证据表明，非病毒载体的开发已取得成功，从而产生了能够避开几乎所有主要转染障碍的系统。评估非病毒和病毒载体克服特定细胞屏障的能力表明，病毒载体的最大优势可能与病毒DNA有关，病毒DNA的转录效率比质粒DNA高得多。该领域的进一步研究应该能够开发出与病毒载体一样有效转染的非病毒载体。
Problems related to the safety and efficacy of gene therapies have checked the enthusiasm once surrounding this field, though it remains a promising approach for the treatment of numerous diseases. Despite the high transfection efficiencies attainable using viral vectors, manufacturing difficulties. safety concerns, and limitations related to targeting and plasmid size have prompted considerable research into the development of non-viral vectors. Non-viral vectors demonstrate low toxicity, low, immunogenicity, and ease of manufacture. However, they have not yet achieved the transfection efficiencies displayed by viruses. The inability to explain or predict transfection efficiencies results, in part, from. insufficient understanding of the intracellular processes involved in gene delivery. increasingly, research has been undertaken to probe the processes involved in overcoming the major obstacles to vector-mediated transfection: (1) internalization, (2) intracellular trafficking, (3) escape to he cytosol, (4) nuclear translocation, and (5) gene transcription/expression. This paper reviews and compares the pathways and techniques involved in successful viral and non-viral transfection. In addition, this review provides evidence that non-viral vector development has been pursued successfully thus jar, producing systems capable of evading almost all major obstacles to transfection. Evaluating the abilities of non-viral and viral vectors to overcome specific cellular barriers reveals that the greatest advantage of viral vectors may be related to viral DNA, which is transcribed considerably more efficiently than plasmid DNA. Further study in this area should enable the development of non-viral vectors that transfect as efficiently as viral vectors.