Target delivery of a gene into the brain using the RVG29-oligoarginine peptide

The development of non-viral delivery systems that are capable of mediating an efficient, exclusive, and non-invasive transfer of DNA across the blood-brain barrier into the brain is challenging, but essential for the clinical application of gene therapy to brain diseases. Compared with other non-viral DNA carriers (e.g., lipids or polymers), peptide-based DNA delivery systems have many advantages including the ease of synthesis, low immunogenicity, biocompatibility, and biodegradability in vivo. However, all of the existing peptide-based vehicles for DNA delivery lack selectivity toward cells or tissues, which largely limited their applications in vivo. In this study, we demonstrated that an RVG29-9rR peptide-based DNA delivery system was able to transfect Neuro 2a cells in vitro more efficiently and specifically than Lipofectamine LTX & Plus, one of the most efficient commercially available transfection reagents. More significantly, the peptide mediated efficient and brain-targeting reporter gene expression after intravenous injection into mice. Thus, the results herein suggest a new strategy for brain-targeting DNA delivery in vivo.