The Application of Nucleic Acid Nanomaterials in the Treatment of Mitochondrial Dysfunction

Abstract: Mitochondrial dysfunction is considered highly related to the development and progression of diseases, including cancer, metabolism disturbance, and neurodegeneration. Traditional pharmacological approach for mitochondrial dysfunction treatment has off-target and dose-dependent side effects, which leads to the emergence of mitochondrial gene therapy by regulating coding or noncoding genes by using nucleic acid sequences such as oligonucleotides, peptide nucleic acids, rRNA, siRNA, etc. To avoid size heterogeneity and potential cytotoxicity of the traditional delivery vehicle like liposome, framework nucleic acids have shown promising potentials. First, special spatial structure like tetrahedron allows entry into cells without transfection reagents. Second, the nature of nucleic acid provides the editability of framework structure, more sites and methods for drug loading and targeted sequences linking, providing efficient transportation and accurate targeting to mitochondria. Third, controllable size leads a possibility to go through biological barrier such as the blood-brain barrier, reaching the central nervous system to reverse mitochondria-related neurodegeneration. In addition, it's biocompatibility and physiological environmental stability open up the possibility of in vivo treatments for mitochondrial dysfunction. Furthermore, we discuss the challenges and opportunities of framework nucleic acids-based delivery systems in mitochondrial dysfunction.