Abstract
BackgroundPeptide/DNA complexes have great potential as non-viral methods for gene delivery. Despite promising results for peptide-mediated gene delivery technology, an effective systemic peptide-based gene delivery system has not yet been developed.MethodsThis study used pCMV-Luc as a model gene to investigate the biodistribution and the in vivo efficacy of arginine peptide-mediated gene delivery by polymerase chain reaction (PCR).ResultsPlasmid DNA was detected in all organs tested 1 h after intraperitoneal administration of arginine/DNA complexes, indicating that the arginine/DNA complexes disseminated widely through the body. The plasmid was primarily detected in the spleen, kidney, and diaphragm 24 h post administration. The mRNA expression of plasmid DNA was noted in the spleen, kidney, and diaphragm for up to 2 weeks, and in the other major organs, for at least 1 week. Blood clearance studies showed that injected DNA was found in the blood as long as 6 h after injection.ConclusionsTaken together, our results demonstrated that arginine/DNA complexes are stable in blood and are effective for in vivo gene delivery. These findings suggest that intraperitoneal administration of arginine/DNA complexes is a promising tool in gene therapy.
Highlights
Peptide/DNA complexes have great potential as non-viral methods for gene delivery
Biodistribution of intraperitoneally administered plasmid DNA The biodistribution of the plasmid DNA was studied after intraperitoneal administration in mice using polymerase chain reaction (PCR) analysis. pCMV-Luc was chosen as a target plasmid
Mice were injected with arginine/DNA complexes prepared with 100 μg plasmid DNA at an N/P ratio of 3:1 and were sacrificed at various time points
Summary
Peptide/DNA complexes have great potential as non-viral methods for gene delivery. Cell-penetrating peptides (CPPs) have been widely shown to transfer macromolecules into living cells [1,2]. Several of these peptides have been identified, such as Tat [3], Antp [4], and VP22 [5]. Most CPPs contain at least 1 basic amino acid residue such as arginine or lysine, suggesting that basic amino acids are critical motifs for the efficient delivery of exogenous biomolecules into cells [13,14]. The authors have focused on the development of an arginine peptide-mediated gene delivery system after previously demonstrating that a short arginine peptide (R15) is able to condense plasmid DNA into small complexes
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