Interaction of reducible polypeptide gene delivery vectors with supported lipid bilayers: pore formation and structure-function relationships

Real-time atomic force microscopy (AFM) in aqueous buffer has been used to probe interactions of synthetic disulfide-linked polypeptide gene delivery vectors with supported phospholipid bilayers. Disruption of the membranes was apparent in AFM, and the extent of surface heterogeneity and hole (pore) formation was evaluated by depth and area-profiling image analysis. The overall extent of membrane disruption varied with the reducible polycation peptide sequence and block structure and was found to be correlated with the overall degree of transgene expression in two representative cell lines. © 2010 The Royal Society of Chemistry

Combination dual responsive polypeptide vectors for enhanced gene delivery.

Variation in amino acid sequences on a disulfide-linked polypeptide backbone generates differing pK(a) vectors for DNA delivery, which release nucleic acids under reducing conditions and transfect cells with greater efficacy than non-reducible or non-variable pK(a) analogues

Multicomponent synthetic polymers with viral-mimetic chemistry for nucleic acid delivery.

The ability to deliver genetic material for therapy remains an unsolved challenge in medicine. Natural gene carriers, such as viruses, have evolved sophisticated mechanisms and modular biopolymer architectures to overcome these hurdles. Here we describe synthetic multicomponent materials for gene delivery, designed with features that mimic virus modular components and which transfect specific cell lines with high efficacy. The hierarchical nature of the synthetic carriers allows the incorporation of membrane-disrupting peptides, nucleic acid binding components, a protective coat layer, and an outer targeting ligand all in a single nanoparticle, but with functionality such that each is utilized in a specific sequence during the gene delivery process. The experimentally facile assembly suggests these materials could form a generic class of carrier systems that could be customized for many different therapeutic settings

Multicomponent Synthetic Polymers with Viral-Mimetic Chemistry for Nucleic Acid Delivery

The ability to deliver genetic material for therapy remains an unsolved challenge in medicine. Natural gene carriers, such as viruses, have evolved sophisticated mechanisms and modular biopolymer architectures to overcome these hurdles. Here we describe synthetic multicomponent materials for gene delivery, designed with features that mimic virus modular components and which transfect specific cell lines with high efficacy. The hierarchical nature of the synthetic carriers allows the incorporation of membrane-disrupting peptides, nucleic acid binding components, a protective coat layer, and an outer targeting ligand all in a single nanoparticle, but with functionality such that each is utilized in a specific sequence during the gene delivery process. The experimentally facile assembly suggests these materials could form a generic class of carrier systems that could be customized for many different therapeutic settings