Vilcapoma Javier, Patel Akul, Chandrasekaran Arun Richard, Halvorsen Ken
bioRxiv. 2023 Mar 6:2023.03.06.531312. doi: 10.1101/2023.03.06.531312.
The potential for using DNA nanostructures for drug delivery applications requires understanding and ideally tuning their biostability. Here we investigate how biological degradation varies with size of a DNA nanostructure. We designed DNA tetrahedra of three edge lengths ranging from 13 to 20 bp and analyzed nuclease resistance for two nucleases and biostability in fetal bovine serum. We found that DNase I had similar digestion rates across sizes but appeared to incompletely digest the smallest tetrahedron, while T5 exonuclease was notably slower to digest the largest tetrahedron. In fetal bovine serum, the 20 bp tetrahedron was degraded ~four times faster than the 13 bp. These results show that DNA nanostructure size can influence nuclease degradation, but suggest a complex relationship that is nuclease specific.
将DNA纳米结构用于药物递送应用的潜力需要了解并理想地调节其生物稳定性。在此，我们研究了生物降解如何随DNA纳米结构的大小而变化。我们设计了三种边长范围为13至20个碱基对的DNA四面体，并分析了两种核酸酶的核酸酶抗性以及在胎牛血清中的生物稳定性。我们发现，DNase I对不同大小的四面体具有相似的消化速率，但似乎不能完全消化最小的四面体，而T5核酸外切酶消化最大的四面体的速度明显较慢。在胎牛血清中，20个碱基对的四面体的降解速度比13个碱基对的快约四倍。这些结果表明，DNA纳米结构的大小会影响核酸酶降解，但提示了一种核酸酶特异性的复杂关系。
