Localized, direct plasmid gene delivery in vivo:: prolonged therapy results in reproducible tissue regeneration

Localized, direct plasmid gene delivery in vivo:: prolonged therapy results in reproducible tissue regeneration
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DOI:
10.1038/10473
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发表时间:
1999-07-01
期刊:
影响因子:
82.9
通讯作者:
Goldstein, S
Goldstein, S
中科院分区:
医学1区
文献类型:
--
作者:
Bonadio, J;Smiley, E;Goldstein, S

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无法以短暂但持续的方式局部递送生长因子是组织再生的重大障碍。能够长时间定位质粒基因传递的系统可能具有较低的毒性,并且非常适合生长因子治疗。我们使用骨再生作为体内终点,研究了从物理捕获在聚合物基质(基因激活基质)中的基因传递质粒基因的效力。在骨损伤部位植入基因激活基质与质粒 DNA 的保留和表达至少 6 周相关,并且与以稳定、可重复、剂量和时间依赖的方式诱导数厘米的正常新骨相关。
The inability to deliver growth factors locally in a transient but sustained manner is a substantial barrier to tissue regeneration. Systems capable of localized plasmid gene delivery for prolonged times may offer lower toxicity and should be well-suited for growth factor therapeutics. We investigated the potency of plasmid gene delivery from genes physically entrapped in a polymer matrix (gene activated matrix) using bone regeneration as the endpoint in vivo. implantation of gene activated matrices at sites of bone injury was associated with retention and expression of plasmid DNA for at least 6 weeks, and with the induction of centimeters of normal new bone in a stable, reproducible, dose- and time-dependent manner.