Photochemically induced gene silencing using PNA-peptide conjugates.
The potential for exploration of peptide nucleic acid (PNA) as an experimental and therapeutic regulator of gene expression has been hampered by a poor delivery and a lack of site-specific targeting. In the present study, we have developed an efficient strategy for nuclear delivery of PNA by combining cationically charged PNA-peptide conjugates and photochemical internalization (PCI) technology. When using the S100A4 gene as a model system, a consistent downregulation to around 10% remaining protein signal was obtained in three selected cell lines. Furthermore, a dose-dependent and time-dependent inhibition of the S100A4 protein was demonstrated. A main benefit of the strategy proposed is the possibility of site-specific targeting.
Bøe
S
S
Department of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital, Montebello, NO-0310 Oslo, Norway. sigurdbo@raidum.uio.no
Hovig
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E
D000595:Amino Acid Sequence; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism; D015536:Down-Regulation; D004705:Endocytosis; D015870:Gene Expression / Q000187:drug effects*; D020868:Gene Silencing; D018390:Gene Targeting / Q000379:methods*; D006801:Humans; D008969:Molecular Sequence Data; D020135:Peptide Nucleic Acids / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D010455:Peptides / Q000737:chemistry; D010777:Photochemistry; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000032:analysis / Q000037:antagonists & inhibitors / Q000235:genetics; D014162:Transfection / Q000379:methods*
D020135:Peptide Nucleic Acids; D010455:Peptides; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C077591:S100A4 protein, human