Efficient active transport of gene nanocarriers to the cell nucleus
Efficient active transport of gene nanocarriers to the cell nucleus
复制标题
DOI：
10.1073/pnas.0636277100
复制
发表时间：
2003-04-01
影响因子：
11.1
通讯作者：
Hanes, J
中科院分区：
文献类型：
--
作者：
Suh, J;Wirtz, D;Hanes, J
对治疗基因载体的细胞内转运知之甚少，限制了有效新载体的合理设计。我们使用活细胞实时多粒子跟踪来量化数百个单独的非病毒 DNA 纳米载体的细胞内运输，分辨率为 5 纳米和 33 毫秒。自然界中几种最有效的 DNA 病毒和非病毒聚乙烯亚胺/DNA 纳米复合物之间的意外相似之处被揭示，包括运动蛋白驱动的通过细胞质向微管上细胞核的运输。活跃的基因载体运输导致几分钟内有效的核周积累。这些结果提供了直接证据来反驳人们的普遍看法，即非病毒基因载体的效率由于需要相对缓慢地随机扩散通过细胞质到细胞核而显着降低，相反，将合理载体设计的注意力集中在克服核周积累下游的障碍上。
The intracellular transport of therapeutic gene carriers is poorly understood, limiting the rational design of efficient new vectors. We used live-cell real-time multiple particle tracking to quantify the intracellular transport of hundreds of individual nonviral DNA nanocarriers with 5-nm and 33-ms resolution. Unexpected parallels between several of nature's most efficient DNA viruses and nonviral polyethylenimine/DNA nanocomplexes were revealed to include motor protein-driven transport through the cytoplasm toward the nucleus on microtubules. Active gene carrier transport led to efficient perinuclear accumulation within minutes. The results provide direct evidence to dispute the common belief that the efficiency of nonviral gene carriers is dramatically reduced because of the need for their relatively slow random diffusion through the cell cytoplasm to the nucleus and, instead, focuses the attention of rational carrier design on overcoming barriers downstream of perinuclear accumulation.