The potential of extrachromosomal replicating vectors for gene therapy
The potential of extrachromosomal replicating vectors for gene therapy
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DOI：
10.1016/0168-9525(96)40049-x
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发表时间：
1996-11-01
影响因子：
11.4
通讯作者：
Calos, MP
中科院分区：
文献类型：
--
作者：
Calos, MP
DNA载体在靶细胞中的持久性在大多数基因治疗应用中是有利的。特别是当靶细胞正在增殖时，载体的寿命将取决于载体与染色体的整合或载体复制和保留染色体外的能力。以非随机方式有效整合的载体目前是不可用的，而那些可以在染色体外复制的载体提供了一个主要的替代策略。有几类这样的载体正在开发中，它们携带了延长哺乳动物细胞核中DNA保留的机制，也延长了载体在非增殖细胞中的寿命。载体利用染色体或病毒元件介导复制和保留，并具有大容量的插入感兴趣的基因。我讨论了这些载体的艺术状态，包括它们在基因治疗中未来使用的资产和限制。
Persistence of DNA vectors in target cells is advantageous in most applications of gene therapy. Particularly when target cells are undergoing proliferation, vector longevity will depend on either the integration of the vector into the chromosomes or the ability of the vector to replicate and be retained extrachromosomally. Vectors that efficiently integrate in a nonrandom fashion are currently unavailable, and those that can replicate extrachromosomally provide a major alternative strategy. Several classes of such vectors are under development, carrying mechanisms for prolonging DNA retention in mammalian nuclei that extend vector lifetime in non-proliferating cells as well. The vectors utilize either chromosomal or viral elements to mediate replication and retention, and have a large size capacity for insertion of genes of interest. I discuss the state of the art for these vectors, including the assets and limitations of their future use in gene therapy.