Department of Biochemistry and Molecular Biology, Iowa State University, Ames, IA, 50011, USA.
Department of Genetics, Development, and Cell Biology, Iowa State University, Ames, IA, 50011, USA.
Sci Rep. 2023 Aug 10;13(1):12961. doi: 10.1038/s41598-023-39777-0.
Nucleic acid nanoparticles are playing an increasingly important role in biomolecular diagnostics and therapeutics as well as a variety of other areas. The unique attributes of self-assembling DNA nanoparticles provide a potentially valuable addition or alternative to the lipid-based nanoparticles that are currently used to ferry nucleic acids in living systems. To explore this possibility, we have assessed the ability of self-assembling DNA nanoparticles to be constructed from complete gene cassettes that are capable of gene expression in vitro. In the current report, we describe the somewhat counter-intuitive result that despite extensive crossovers (the stereochemical analogs of Holliday junctions) and variations in architecture, these DNA nanoparticles are amenable to gene expression as evidenced by T7 RNA polymerase-driven transcription of a reporter gene in vitro. These findings, coupled with the vastly malleable architecture and chemistry of self-assembling DNA nanoparticles, warrant further investigation of their utility in biomedical genetics.
核酸纳米颗粒在生物分子诊断和治疗以及其他各种领域中发挥着越来越重要的作用。自组装 DNA 纳米颗粒的独特属性为脂质纳米颗粒提供了一种潜在的有价值的补充或替代，脂质纳米颗粒目前用于在活系统中输送核酸。为了探索这种可能性，我们已经评估了自组装 DNA 纳米颗粒从能够在体外表达基因的完整基因盒构建的能力。在当前的报告中，我们描述了一个有些违反直觉的结果，尽管存在广泛的交叉（霍利迪结的立体化学类似物）和结构变化，但这些 DNA 纳米颗粒可进行基因表达，这表现在 T7 RNA 聚合酶体外驱动报告基因转录。这些发现，加上自组装 DNA 纳米颗粒的结构和化学的高度可塑，证明了它们在生物医学遗传学中的应用具有进一步研究的价值。
