Peptide-mediated cellular delivery of antisense oligonucleotides and their analogues.
Improving the delivery of synthetic oligonucleotides and their analogues into cells is an important goal in the full development of antisense technology for control of gene expression in cell culture and in vivo. This review describes the harnessing of certain peptides, either as noncovalent complexes or as covalent conjugates, to enhance the delivery of antisense oligonucleotides into cells and/or to affect their cell localization. Phosphodiester and phosphorothioate oligonucleotides are included as well as peptide nucleic acids (PNAs), analogues of oligonucleotides where the negatively charged phosphate backbone is replaced by a neutral amide linkage. This review contains a critical evaluation of claims for certain peptide-oligonucleotide conjugates to translocate into cultured cells by a non-energy-dependent nonendosomal route. In addition, the available evidence for the utility of stable versus nonstable linkages between peptide and oligonucleotide or PNA is discussed.
Gait
Michael J
MJ
Medical Research Council, Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, United Kingdom. mgait@mrc-lmb.cam.ac.uk
D000818:Animals; D001419:Bacteria / Q000187:drug effects / Q000254:growth & development; D001692:Biological Transport; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage* / Q000378:metabolism; D020135:Peptide Nucleic Acids / Q000008:administration & dosage* / Q000378:metabolism; D010455:Peptides / Q000008:administration & dosage* / Q000378:metabolism
D016376:Oligonucleotides, Antisense; D020135:Peptide Nucleic Acids; D010455:Peptides