title: An influenza virus-inspired polymer system for the timed release of siRNA.
abstract: Small interfering RNA silences specific genes by interfering with mRNA translation, and acts to modulate or inhibit specific biological pathways; a therapy that holds great promise in the cure of many diseases. However, the naked small interfering RNA is susceptible to degradation by plasma and tissue nucleases and due to its negative charge unable to cross the cell membrane. Here we report a new polymer carrier designed to mimic the influenza virus escape mechanism from the endosome, followed by a timed release of the small interfering RNA in the cytosol through a self-catalyzed polymer degradation process. Our polymer changes to a negatively charged and non-toxic polymer after the release of small interfering RNA, presenting potential for multiple repeat doses and long-term treatment of diseases.
authors.affiliation: Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane Queensland 4072, Australia.
authors.forename: Nghia P
authors.initials: NP
authors.lastname: Truong
authors.forename: Wenyi
authors.initials: W
authors.lastname: Gu
authors.forename: Indira
authors.initials: I
authors.lastname: Prasadam
authors.forename: Zhongfan
authors.initials: Z
authors.lastname: Jia
authors.forename: Ross
authors.initials: R
authors.lastname: Crawford
authors.forename: Yin
authors.initials: Y
authors.lastname: Xiao
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Monteiro
mesh_terms: D002384:Catalysis; D018797:Cell Cycle Proteins / Q000378:metabolism; D016923:Cell Death; D045744:Cell Line, Tumor; D019902:Chondrocytes / Q000201:enzymology / Q000473:pathology; D048049:Extracellular Signal-Regulated MAP Kinases; D055785:Gene Knockdown Techniques; D006801:Humans; D008689:Methacrylates / Q000737:chemistry*; D009757:Nylons; D009975:Orthomyxoviridae / Q000378:metabolism*; D010003:Osteoarthritis / Q000201:enzymology / Q000473:pathology; D012516:Osteosarcoma / Q000201:enzymology / Q000473:pathology; D011108:Polymers / Q000737:chemistry*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism*; D013997:Time Factors; D000097869:Polo-Like Kinase 1
chemical_list: D018797:Cell Cycle Proteins; D048049:Extracellular Signal-Regulated MAP Kinases; D008689:Methacrylates; D009757:Nylons; D011108:Polymers; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D000097869:Polo-Like Kinase 1; C407037:poly(2-(dimethylamino)ethyl methacrylate)