ABSTRACT
Gene therapy vectors based on adeno-associated virus (AAV) are currently in clinical trials for numerous disease targets, such as muscular dystrophy, hemophilia, Parkinson's disease, Leber's congenital amaurosis and macular degeneration. Despite its considerable promise and emerging clinical success, several challenges impede the broader implementation of AAV gene therapy, including the prevalence of neutralizing antibodies in the human population, low transduction of a number of therapeutically relevant cell and tissue types, an inability to overcome physical and cellular barriers in vivo and a relatively limited carrying capacity. These challenges arise as the demands we place on AAV vectors are often different from or even at odds with the properties nature bestowed on their parent viruses. Viral-directed evolution-the iterative generation of large, diverse libraries of viral mutants and selection for variants with specific properties of interest-offers an approach to address these problems. Here we outline progress in creating novel classes of AAV variant libraries and highlight the successful isolation of variants with novel and advantageous in vitro and in vivo gene delivery properties.
Subject(s)
Dependovirus/genetics , Directed Molecular Evolution , Gene Transfer Techniques , Genetic Vectors , Animals , Dependovirus/physiology , Disease Models, Animal , Humans , Selection, Genetic , Stem CellsABSTRACT
Fe2O3 shells have been synthesized around Pt cores to create Pt@Fe2O3 core-shell nanoparticles. The synthesis conditions allow control of the shell shape and allow the preparation of both hexagonal shells and spherical shells. 2D cross-sectional TEM images show that the cores are not positioned at the centers of the shells. By rotating the nanoparticles and monitoring the apparent motions of the cores in the 2D cross-sectional images, it is possible to determine quantitatively the radial position of the Pt core with respect to the center of the Fe2O3 shell. The distribution of core positions within the core-shell structures is bimodal. These observations suggest that the Fe2O3 shells grow on the Pt cores by a nucleation process, rather than layer-by-layer growth.
Subject(s)
Crystallization/methods , Ferric Compounds/chemistry , Nanostructures/chemistry , Nanostructures/ultrastructure , Platinum/chemistry , Macromolecular Substances/chemistry , Materials Testing , Molecular Conformation , Nanotechnology/methods , Particle Size , Surface PropertiesABSTRACT
Fe(x)Pt(100-x) nanoparticles of varying composition have been synthesized with various shapes and sizes using a high pressure synthesis method which allows control of synthesis conditions, in particular the reaction temperature. Tailoring the shapes and sizes of Fe(x)Pt(1-x) nanoparticles allows one to control a variety of properties that are relevant to the many potential applications of metallic nanoparticles. Shape and composition can be used to control catalytic activity and to achieve high packing density in self-assembled films. Variation of both nanoparticle size and shape has been achieved by using various different solvents. The solvents used in the nanoparticle synthesis can influence the product because they can play a role as surfactants. Using solvents of various types it has been possible to synthesize Fe(x)Pt(100-x) nanoparticles with a variety of shapes including spherical, rod-like, cubic, hexagonal and high aspect ratio wires. Control of nanoparticle shape opens the door to their being used in various technological applications for which spherical nanoparticles are ineffective.
