Nanoscale Science Program, Department of Chemistry, University of North Carolina at Charlotte, Charlotte, NC, USA.
Department of Biological Sciences, University of North Carolina at Charlotte, Charlotte, NC, USA.
Methods Mol Biol. 2023;2709:229-240. doi: 10.1007/978-1-0716-3417-2_15.
Nucleic acid nanoparticles (NANPs) composed of therapeutic DNA, RNA, or a hybrid of both are increasingly investigated for their targeted and tunable immunomodulatory properties. By taking advantage of the NANPs' unique and relatively straightforward self-assembling behavior, nucleic acid sequences can be designed from the bottom-up and specifically tailored to induce certain immune responses in mammalian cells (Johnson et al., Nucleic Acids Res 48:11785-11798, 2020). Although not yet used in the clinic, functionalized NANPs display promising advantages to be included in therapeutic applications. By adjusting the chemical composition of a limited selection of NANPs all sharing the same physicochemical properties, it is demonstrated how substituting RNA strands for different chemical analogs can increase the thermodynamic and enzymatic stability of NANPs. Altering the composition of NANPs also determines the cellular mechanisms which initiate immune responses, therefore impacting the subcellular targeting and delivery efficiency.
核酸纳米颗粒（NANPs）由治疗性 DNA、RNA 或两者的混合物组成，因其具有靶向和可调免疫调节特性而受到越来越多的研究。通过利用 NANPs 的独特且相对简单的自组装行为，可以从底层设计核酸序列，并专门设计用于在哺乳动物细胞中诱导特定免疫反应（Johnson 等人，Nucleic Acids Res 48:11785-11798, 2020）。尽管尚未在临床上使用，但功能化的 NANPs 具有在治疗应用中被包含的有希望的优势。通过调整具有相同物理化学性质的有限选择的 NANPs 的化学组成，证明了用不同的化学类似物替代 RNA 链如何提高 NANPs 的热力学和酶稳定性。改变 NANPs 的组成还决定了引发免疫反应的细胞机制，因此影响亚细胞靶向和递药效率。
