Progress has been made in the study of gene silencing at the National Nano-Center

recently, Ding Baoquan, a researcher at the
National Nanoscience Center in China, made progress in the study of self-assembled gene silencing systems based on nucleic acids for cancer therapy, using Thebrached Antisense and siRNA Co-assembled Nanoplatform. The title for Combined Gene Silencing and Tumor Therapy is published in Angewandte Chemie International Edition (DOI: 10.1021/anie.202011174).
In recent years, the research of gene silencing system in the field of tumor treatment has been widely reported, mainly through various types of cation lipids, polymers and inormeric nanoparticles as carriers to deliver antonymic nucleic acids or small interference RNA, to silence tumor-related genes, to achieve the purpose of inhibiting tumor growth. Nucleic acid self-assembly system based on base complementary pairing can be designed as nanostructures of different sizes and shapes, and various gene therapy drugs of the same nucleic acid can also be assembled by way of base complementary pairing, thus making it possible to build a gene therapy system based on nucleic acid self-assembly.
of the project, Ding Bao's entire team has made a series of advances in the delivery of gene therapy drugs using multifunction nucleic acid nanostructures (Journal of American Chemical Society 2019, 141, 19032; Angewandte Chemie International Edition 2018, 57, 15486; Nano Letters 2018, 18, 3328). Nucleic acid self-assembly structure has the characteristics of controlled size, fixed-point modification and bio-compatible, and is an excellent drug carrier. In order to further improve the utilization efficiency of nucleic acid molecules, it is important to construct a kind of gene therapy compound nanosystructure composed of nucleic acid drugs with drug carrier efficacy.
On the basis of the previous research, Dingbao's whole team realized the coassembly assembly of antisocial nucleic acids and small interfering RNA by introducing small molecule-coupled branch-chain nucleic acid drugs, and constructed a class of gene therapy nucleic acid nanocomposates that are both vectors and drugs for the joint treatment of tumors. To study the preparation of branch chain antisumatic nucleic acids (7AS) using ring-shaped supermolegator β circle dextry for the kernel by copper-free click reaction co-priced anthocific nucleic acid sequence. At the same time, the 3' end of the classic small interfering RNA is extended to create an RNA sequence that can be partially paired with an antisant nucleic acid as a base-recognized connector (siRNAL). Base identification and co-assembly of the branch chain antisystic nucleic acid with the small interference RNA extended at the end of the 3' to obtain the nucleic acid nanocomposum. Through the main object identification mechanism of supermolebone system, the targeted folic acid ligation and connotation escape peptide modified by alkalic acid modification are introduced in the gene therapy nucleic acid nanocompos complex, and the optional internalization of target cells and the subsequent intension escape process are realized. Under the recognition and cutting of RNase H enzyme in cells, branch chain antisane nucleic acids and small interfering RNA are gradually released to identify and cut mRNAs encoded by the tumor-related gene PPK1, to achieve joint gene therapy and inhibit the proliferation of tumor cells. At the live level of mice, the gene-treated nucleic acid nanocomposome showed obvious tumor-rich effect and low immunogenicity. At a dose of 1.2 mg/kg, significant downward levels of the tumor-related gene PPK1 were observed to inhibit tumor growth. By constructing branch-chain nucleic acid drugs, using nucleic acid self-assembly and supermolecule main object recognition, the study prepares gene therapy nucleic acid nanocomposomes with targeted recognition ability and response to specific biomolecules in cells, and realizes the precise treatment of target genes, providing a new research strategy for the diagnosis and treatment of malignant tumors and other diseases.
the first author of the paper is Liu Jianbing, an associate researcher at the National Nano Center, and the author of the paper is Ding Baoquan and Liu Jianbing. The research work is supported by the National Natural science
, the national strategic pilot science and
, and the key research program of cutting-edge science. (Source: National Nanoscience Center)
Related paper information:chain antisocial nucleic acids and small interference RNA co-assembled to build a gene therapy type nucleic acid nanocomposing structure, targeting tumors to achieve tumor growth inhibition