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Engineering synthetic vectors for improved DNA delivery: insights from intracellular pathways.
Annual Review of Biomedical Engineering ( IF 9.7 ) Pub Date : 2004-07-17 , DOI: 10.1146/annurev.bioeng.6.040803.140203
Charles M Roth 1 , Sumati Sundaram
Affiliation  

Significant progress has been made in the area of nonviral gene delivery to date. Yet, synthetic vectors remain less efficient by orders of magnitude than their viral counterparts. Research continues toward unraveling and overcoming various barriers to the efficient delivery of DNA, whether in plasmid form encoding a gene or as an oligonucleotide for the selective inhibition of target gene expression. Novel components for overcoming these hurdles are continually being incorporated into the design of synthetic vectors, leading to increasingly more virus-like particles. Despite these advances, general principles defining the design of synthetic vectors are yet to be developed fully. A more quantitative analysis of the cellular uptake and intracellular processing of these vectors is required for the rational manipulation of vector design. Mathematical frameworks with a more conceptual basis will help obtain an integrated perspective on these complex systems. In this review, we critically examine the progress made toward the improved design of synthetic vectors by the strategic exploitation of intracellular mechanisms and explore newer possibilities to overcome obstacles in the practical realization of this field.

中文翻译:

工程合成载体以改善DNA传递:来自细胞内途径的见解。

迄今为止,在非病毒基因递送领域已取得重大进展。但是,合成载体的效率仍然比病毒载体低几个数量级。无论是编码基因的质粒形式还是作为选择性抑制靶基因表达的寡核苷酸,研究一直在努力探索和克服各种障碍,以有效地传递DNA。克服这些障碍的新颖成分不断地被整合到合成载体的设计中,从而导致越来越多的病毒样颗粒。尽管取得了这些进步,但定义合成载体设计的一般原则仍未得到充分发展。这些载体的细胞摄取和细胞内加工的更定量分析对于载体设计的合理操作是必需的。具有更多概念基础的数学框架将有助于获得有关这些复杂系统的综合观点。在这篇综述中,我们批判性地研究了通过细胞内机制的战略性利用来改进合成载体设计的进展,并探索了克服这一领域实际实现障碍的新可能性。
更新日期:2019-11-01
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