Abstract
The blood-brain barrier (BBB) exerts its central nervous system (CNS) protective function as it hinders the delivery of diagnostic and therapeutic agents to the brain. Gene therapy could be applied in conquering brain diseases such as neurodegenerative diseases and brain tumors by up- or down-regulating expression of diseased proteins. With the development of nanotechnology during the last thirty years, the nanocarriers for delivering drugs including gene medicines make it possible to transport drugs across the BBB. The nonviral nano-scaled gene delivery systems hold great promise for treating brain diseases due to their safety and convenience. Several brain targeting strategies, such as adsorptive- and receptor-mediated pathways have been developed to improve the brain targeting efficiency of non-viral gene delivery systems. In this review, the non-viral nanocarriers are focused for gene delivery and several possible strategies are discussed to achieve brain targeting effects. Finally, the applications of gene therapy in several brain diseases will be introduced.
Keywords: Blood-brain barrier, brain-targeting, gene therapy, nanoparticles, non-viral gene delivery, receptor-mediated endocytosis, central nervous system, herpes virus, lentiviruses, adeno-associated, immuno-genicity, viral cationic liposome, polymer vectors, lipoplexes, polyplexes, adsorptive-mediated endocytosis, Parkinson's disease, Alzheimer's disease, brain tumors, monocytes, Cationic Lipids, attenuation, hippocampus, Polyethylenimine (PEI), Polyamidoamine (PAMAM), red blood cells (RBCs), Adsorptive Mediated Endocytosis, HIV-1 Trans-Activating Transcriptional Activator, Antennapedia Peptide, Low Molecular Weight Protamine (LMWP), Transferrin Receptors, Lactoferrin (Lf) Receptors, Insulin Receptors, Acetylcholine Receptor, Low Density Lipoprotein (LDL) Receptor Family, Leptin Receptors, Dopamine, Neurotrophic Factors
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