Rationally designed synthetic vectors for therapeutic nucleic acid delivery against human cytomegalovirus infection

Abstract

RNA therapy represents a great way to precisely regulate cellular processes by modulating the gene expression. Despite this potential, a profound gap exists in our knowledge of how to subsequently deliver these RNAs into the specific target cells and turn therapeutically active RNAs into practical medicines. An advanced series of interlocked, thermodynamically self-regulated processes that enable the precise assembly of functional synthetic carriers of siRNA to the target cells in vivo was developed. To demonstrate the efficacy of this delivery system, we used it to treat human cytomegalovirus (HCMV) infection in a humanized mouse model. In this study, we use small interfering RNA (siRNA) and small complementary RNA (scRNA) to inhibit the expressions of two HCMV genes, IE1 and IE2. The auto-regulated nanocarrier polywraplex with core-shell structure was designed to condense and package these RNAs for delivering. To allow these particles recognize the HCMVinfected cells, a ligand was coupled on the surface of nanoparticle, which would specifically target the HCMV-encoded CX 3 CL 1 chemokine receptor presented in the HCMV-infected cells. The results demonstrated that the polywraplex conjugated with the target molecule CX 3 CL 1 effectively and specifically delivered the siRNA/ scRNA to HCMV infected cells and inhibited virus growth in vitro and in vivo.

Identification and characterization of Varicella Zoster Virus circular RNA in lytic infection

“…Briefly, human fetal tissues (skin and DRG, 18–20 weeks old) were obtained from Advanced Bioscience Resources (ABR). The tissues were washed with 1X PBS, processed, cultured in DMEM–F-12 (1:1) and 2% FBS and grown at 37 °C/5% CO 2 8 , 62 . Tissues were infected with pOka, pOka-M1, and pOka-M2 (100PFU/well).…”