Lipid-mediated delivery of peptide nucleic acids to pulmonary endothelium.
Peptide nucleic acid (PNA) is a DNA/RNA mimic in which the phosphodiester (PO) linkage is replaced with a peptide bond. It has a number of unique properties compared to currently used oligonucleotides including higher affinity towards RNA or DNA target, resistance to nucleases or proteases, and minimal non-specific interactions with proteins. Clinical applications of PNA, however, are limited by its inefficient intracellular delivery. In this study, we have shown that delivery of PNA to pulmonary endothelium in intact mice can be greatly improved via hybridization with a short PO oligonucleotide that serves as a carrier to form complexes with cationic liposomes. We have also shown for the first time that unlike a CpG DNA oligo that is highly proinflammatory, a CG-containing PNA is inert in triggering TNF-alpha response in cultured macrophages and in mice. Thus delivery of PNA to pulmonary endothelium may prove to be a therapeutically useful for the treatment of pulmonary vascular diseases.
Yuan
Xing
X
Center for Pharmacogenetics and Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, 639 Salk Hall, Pittsburgh, PA 15213, USA.
Ma
Zheng
Z
Zhou
Wen
W
Niidome
Takuro
T
Alber
Sean
S
Huang
Leaf
L
Watkins
Simon
S
Li
Song
S
D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D018899:CpG Islands; D017931:DNA Primers; D004727:Endothelium / Q000378:metabolism; D008055:Lipids / Q000008:administration & dosage*; D008168:Lung / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D020135:Peptide Nucleic Acids / Q000008:administration & dosage*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D017931:DNA Primers; D008055:Lipids; D020135:Peptide Nucleic Acids; D014409:Tumor Necrosis Factor-alpha