Delivery of siRNA Therapeutics: Barriers and Carriers View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2010-06-11

AUTHORS

Jie Wang, Ze Lu, M. Guillaume Wientjes, Jessie L.-S. Au

ABSTRACT

RNA interference is a naturally occurring endogenous regulatory process where short double-stranded RNA causes sequence-specific posttranscriptional gene silencing. Small interference RNA (siRNA) represents a promising therapeutic strategy. Clinical evaluations of siRNA therapeutics in locoregional treatment settings began in 2004. Systemic siRNA therapy is hampered by the barriers for siRNA to reach their intended targets in the cytoplasm and to exert their gene silencing activity. The three goals of this review were to provide an overview of (a) the barriers to siRNA delivery, from the perspectives of physicochemical properties of siRNA, pharmacokinetics and biodistribution, and intracellular trafficking; (b) the non-viral siRNA carriers including cell-penetrating peptides, polymers, dendrimers, siRNA bioconjugates, and lipid-based siRNA carriers; and (c) the current status of the clinical trials of siRNA therapeutics. More... »

PAGES

492-503

References to SciGraph publications

  • 2004-10-07. Gene knockdown with intrathecal siRNA of NMDA receptor NR2B subunit reduces formalin-induced nociception in the rat in GENE THERAPY
  • 2004-12-23. RNAi-mediated gene-targeting through systemic application of polyethylenimine (PEI)-complexed siRNA in vivo in GENE THERAPY
  • 2009-05-03. Intravaginal gene silencing using biodegradable polymer nanoparticles densely loaded with small-interfering RNA in NATURE MATERIALS
  • 2005-05-22. Antibody mediated in vivo delivery of small interfering RNAs via cell-surface receptors in NATURE BIOTECHNOLOGY
  • 2005-07-24. Potent and persistent in vivo anti-HBV activity of chemically modified siRNAs in NATURE BIOTECHNOLOGY
  • 2006-01-05. Design and cloning strategies for constructing shRNA expression vectors in BMC BIOTECHNOLOGY
  • 2008-03-26. Sequence- and target-independent angiogenesis suppression by siRNA via TLR3 in NATURE
  • 2010-03-21. Evidence of RNAi in humans from systemically administered siRNA via targeted nanoparticles in NATURE
  • 2006-03-26. RNAi-mediated gene silencing in non-human primates in NATURE
  • 2009-02. Knocking down barriers: advances in siRNA delivery in NATURE REVIEWS DRUG DISCOVERY
  • 2009-08-23. Systemic administration of optimized aptamer-siRNA chimeras promotes regression of PSMA-expressing tumors in NATURE BIOTECHNOLOGY
  • 1998-02. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans in NATURE
  • 2004-12-26. Inhibition of respiratory viruses by nasally administered siRNA in NATURE MEDICINE
  • 2005-06. c-Myc-regulated microRNAs modulate E2F1 expression in NATURE
  • 2003-09. Drug Delivery and Transport to Solid Tumors in PHARMACEUTICAL RESEARCH
  • 2000-03-01. Rapid crossing of the pulmonary endothelial barrier by polyethylenimine/DNA complexes in GENE THERAPY
  • 2006-04-20. A novel siRNA-lipoplex technology for RNA interference in the mouse vascular endothelium in GENE THERAPY
  • 2006-05. Fatality in mice due to oversaturation of cellular microRNA/short hairpin RNA pathways in NATURE
  • 2005-04. Different delivery methods—different expression profiles in NATURE METHODS
  • 2009-01-21. The promises and pitfalls of RNA-interference-based therapeutics in NATURE
  • 2006-06-25. Cell type–specific delivery of siRNAs with aptamer-siRNA chimeras in NATURE BIOTECHNOLOGY
  • 2004-11. Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs in NATURE
  • Journal

    TITLE

    The AAPS Journal

    ISSUE

    4

    VOLUME

    12

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1208/s12248-010-9210-4

    DOI

    http://dx.doi.org/10.1208/s12248-010-9210-4

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1006062010

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/20544328


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