A research team led by Prof. Baoquan Ding from the National Center for Nanoscience and Technology (NCNST) proposed a facile strategy for tumor therapy based on gene silencing assisted by nucleic acid self-assembly. The study was published in Angew. Chem. Int. Ed., entitled “Branched Antisense and siRNA Co-assembled Nanoplatform for Combined Gene Silencing and Tumor Therapy” (DOI: 10.1021/anie.202011174), link to the paper: https://onlinelibrary.wiley.com/doi/10.1002/anie.202011174.
According to the literature, cationic liposomes, polymer and inorganic nanoparticles are widely employed as carriers to deliver antisense or small interfering RNA (siRNA) to silence tumor related genes and inhibit tumor growth. Nucleic acid self-assembly system constructed by complementary base pairing can be designed into nanostructures of different sizes and shapes. Meanwhile, gene therapy drugs can also be co-assembled by complementary base pairing, which makes the construction of gene therapy system based on nucleic acid self-assembly possible.
Previously, Prof. Ding has constructed various delivery systems of gene therapy drugs based on multifunctional nucleic acid nanostructures (J. Am. Chem. Soc. 2019, 141, 19032; Angew. Chem. Int. Ed. 2018, 57, 15486; Nano Lett. 2018, 18, 3328). It is well known nucleic acid self-assembly structures can be utilized as drug carriers due to controlled size, site-specific modification and biocompatibility. To further improve the utilization of nucleic acid, it is very attractive to construct a novel gene therapy system composed of nucleic acid drugs and also acting as drug carriers.
Recently, Prof. Ding reported a facile strategy for construction of branched antisense DNA and siRNA co-assembled nanoplatform for combined gene silencing in vitro and in vivo. In this design, the branched antisense can efficiently capture siRNA with 3’ overhangs through DNA-RNA hybridization. After being equipped with an active targeting group and an endosomal escape peptide by host-guest interaction, the tailored nucleic acid nanostructure functions efficiently as both delivery carrier and therapeutic cargo, which is released by endogenous RNase H digestion. The multifunctional nucleic acid nanosystem elicits an efficient inhibition of tumor growth based on the combined gene silencing of the tumor-associated gene polo-like kinase 1 (PLK1). This biocompatible nucleic acid nanoplatform presents a new strategy for the development of gene therapy.
The research was supported by the National Natural Science Foundation of China, the Strategic Priority Research Program of CAS, the Key Research Program of Frontier Science, CAS, and so on.
Figure. Gene therapeutic nucleic acid nanocomposites constructed by co-assembly of branched antisense and siRNA for tumor therapy.