title: The delivery of therapeutic oligonucleotides.
abstract: The oligonucleotide therapeutics field has seen remarkable progress over the last few years with the approval of the first antisense drug and with promising developments in late stage clinical trials using siRNA or splice switching oligonucleotides. However, effective delivery of oligonucleotides to their intracellular sites of action remains a major issue. This review will describe the biological basis of oligonucleotide delivery including the nature of various tissue barriers and the mechanisms of cellular uptake and intracellular trafficking of oligonucleotides. It will then examine a variety of current approaches for enhancing the delivery of oligonucleotides. This includes molecular scale targeted ligand-oligonucleotide conjugates, lipid- and polymer-based nanoparticles, antibody conjugates and small molecules that improve oligonucleotide delivery. The merits and liabilities of these approaches will be discussed in the context of the underlying basic biology.
authors.affiliation: UNC Eshelman School of Pharmacy and UNC School of Medicine, University of North Carolina, Chapel Hill, NC 27599, USA arjay@med.unc.edu.
authors.forename: Rudolph L
authors.initials: RL
authors.lastname: Juliano
mesh_terms: D000818:Animals; D018014:Gene Transfer Techniques; D006801:Humans; D008024:Ligands; D009696:Nucleic Acids / Q000627:therapeutic use; D009841:Oligonucleotides / Q000627:therapeutic use*; D011956:Receptors, Cell Surface / Q000378:metabolism
chemical_list: D008024:Ligands; D009696:Nucleic Acids; D009841:Oligonucleotides; D011956:Receptors, Cell Surface