Luo Dan, Li Yougen, Um Soong Ho, Cu Yen
Department of Biological and Environmental Engineering, Cornell University, Ithaca, NY, USA.
Methods Mol Med. 2006;127:115-25. doi: 10.1385/1-59745-168-1:115.
DNA can be used as a generic delivery vector in addition to its genetic role as a antigen expression vector. This is inspired in part by the fact that DNA molecules are true polymers. Surprisingly, DNA molecules have not been used as a delivery vector material. This is probably due to the fact that almost all DNA have only two shapes: linear or circular. This chapter details our efforts in fabricating highly branched dendrimer-like DNA (DL-DNA) that may serve as a multivalent DNA delivery vector. Just like chemical dendrimers, DL-DNA is multi-valent and monodisperse. However, unlike traditional chemical dendrimers, DL-DNA is much larger (~100 nm, generation 4) and can be designed to be nonsymmetric as well. Most importantly, DL-DNA possesses two unique properties: anisotropicity and biodegradability, making multiple, specific conjugations of viral peptides possible. Our method suggests that viral-pep-tide conjugated DL-DNA vectors can deliver genes into cells without any other transfection reagents. This viral-nonviral hybrid system can be further tailored to specific cells by conjugating specific ligands. We believe that such a DL-DNA-based, viral, and nonviral hybrid assembly will provide a new platform for drug delivery in general and gene delivery in particular.
除了作为抗原表达载体的遗传作用外，DNA还可作为一种通用的递送载体。这部分受到DNA分子是真正的聚合物这一事实的启发。令人惊讶的是，DNA分子尚未被用作递送载体材料。这可能是由于几乎所有的DNA只有两种形状：线性或环状。本章详细介绍了我们在制备可能用作多价DNA递送载体的高度分支的树枝状DNA（DL-DNA）方面所做的努力。就像化学树枝状大分子一样，DL-DNA是多价且单分散的。然而，与传统的化学树枝状大分子不同，DL-DNA要大得多（第4代约100纳米），并且也可以设计成不对称的。最重要的是，DL-DNA具有两个独特的特性：各向异性和生物可降解性，使得病毒肽的多重、特异性偶联成为可能。我们的方法表明，病毒肽偶联的DL-DNA载体无需任何其他转染试剂就能将基因导入细胞。通过偶联特定的配体，这种病毒-非病毒杂交系统可以进一步针对特定细胞进行定制。我们相信，这种基于DL-DNA的病毒和非病毒杂交组装体将为一般的药物递送，特别是基因递送提供一个新的平台。
