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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Catalysis
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Cell Cycle Proteins / metabolism
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Cell Death
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Cell Line, Tumor
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Chondrocytes / enzymology
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Chondrocytes / pathology
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Extracellular Signal-Regulated MAP Kinases
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Gene Knockdown Techniques
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Humans
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Methacrylates / chemistry*
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Nylons
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Orthomyxoviridae / metabolism*
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Osteoarthritis / enzymology
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Osteoarthritis / pathology
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Osteosarcoma / enzymology
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Osteosarcoma / pathology
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Polo-Like Kinase 1
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Polymers / chemistry*
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Protein Serine-Threonine Kinases / metabolism
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Proto-Oncogene Proteins / metabolism
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RNA Interference
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RNA, Small Interfering / metabolism*
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Time Factors
Substances
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Cell Cycle Proteins
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Methacrylates
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Nylons
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Polymers
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Proto-Oncogene Proteins
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RNA, Small Interfering
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poly(2-(dimethylamino)ethyl methacrylate)
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Protein Serine-Threonine Kinases
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Extracellular Signal-Regulated MAP Kinases