Chromatooraphic purification of recombinant adenoviral and adeno-associated viral vectors: methods and implications

Chromatooraphic purification of recombinant adenoviral and adeno-associated viral vectors: methods and implications
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DOI:
10.1038/sj.gt.3302611
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发表时间:
2005-10-01
期刊:
影响因子:
5.1
通讯作者:
Loffe, E
Loffe, E
中科院分区:
医学3区
文献类型:
--
作者:
Burova, E;Loffe, E

文献摘要

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近年来,重组腺病毒和腺相关病毒(AAV)载体已被用于许多基因递送方法中。这些载体在临床基因转移中的使用增加了对其表征、生产和纯化的需求。尽管通过密度梯度离心纯化腺病毒或AAV的经典方法在小规模上是有效的,但色谱分离是大规模生产重组腺病毒或AAV的最通用和最有力的方法。本文综述了腺病毒或AAV纯化和工艺开发的不同色谱模式,以及病毒生产的不同纯化步骤的实用性。用于基因治疗的病毒载体的开发的进展,如新的AAV血清型的发现,腺病毒和AAV重靶向和辅助依赖性腺病毒载体的改进的生产,需要进一步开发有效的纯化方法。
In recent years, recombinant adenoviral and adeno-associated viral (AAV) vectors have been exploited in a number of gene delivery approaches. The use of these vectors in clinical gene transfer has increased the demand for their characterization, production and purification. Although the classical method of adenovirus or AAV purification by density gradient centrifugation is effective on a small scale, chromatographic separation is the most versatile and powerful method for large-scale production of recombinant adenovirus or AAV. This review describes different chromatographic modes for adenovirus or AAV purification and process development, as well as the utility of different purification steps for virus production. Advances in the development of viral vectors for gene therapy, such as the discovery of new AAV serotypes, adenoviral and AAV retargeting and improved production of helper-dependent adenoviral vectors, require further development of efficient purification methods.