Journal ArticleDOI
Nonviral Vectors for Gene Delivery
TLDR
Two nonviral gene delivery systems using either biodegradable poly(D,Llactide-co-glycolide) (PLG) nanoparticles or cell penetrating peptide (CPP) complexes have been designed and studied using A549 human lung epithelial cells.Abstract:
The development of nonviral vectors for safe and efficient gene delivery has been gaining considerable attention recently. An ideal nonviral vector must protect the gene against degradation by nuclease in the extracellular matrix, internalize the plasma membrane, escape from the endosomal compartment, unpackage the gene at some point and have no detrimental effects. In comparison to viruses, nonviral vectors are relatively easy to synthesize, less immunogenic, low in cost, and have no limitation in the size of a gene that can be delivered. Significant progress has been made in the basic science and applications of various nonviral gene delivery vectors; however, the majority of nonviral approaches are still inefficient and often toxic. To this end, two nonviral gene delivery systems using either biodegradable poly(D,Llactide-co-glycolide) (PLG) nanoparticles or cell penetrating peptide (CPP) complexes have been designed and studied using A549 human lung epithelial cells. PLG nanoparticles were optimized for gene delivery by varying particle surface chemistry using different coating materials that adsorb to the particle surface during formation. A variety of cationic coating materials were studied and compared to more conventional surfactants used for PLG nanoparticle fabrication. Nanoparticles (~200 nm) efficiently encapsulated plasmids encoding for luciferase (80-90%) and slowly released the same for two weeks. After a delay, moderate levels of gene expression appeared at day 5 for certain positively charged PLG particles and gene expression was maintained for at least two weeks. In contrast, gene expression mediated by polyethyleneimine (PEI) ended at day 5. PLG particles were also significantly lessread more
Citations
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Journal ArticleDOI
Non-viral vectors for gene-based therapy
Hao Yin,Rosemary Lynn Kanasty,Ahmed A. Eltoukhy,Arturo J. Vegas,J. Robert Dorkin,Daniel G. Anderson +5 more
TL;DR: The biological barriers to gene delivery in vivo are introduced and recent advances in material sciences, nanotechnology and nucleic acid chemistry that have yielded promising non-viral delivery systems are discussed, some of which are currently undergoing testing in clinical trials.
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Functionalizing nanoparticles with biological molecules: developing chemistries that facilitate nanotechnology.
Kim E. Sapsford,W. Russ Algar,Lorenzo Berti,Kelly Boeneman Gemmill,Brendan J. Casey,Eunkeu Oh,Michael H. Stewart,Igor L. Medintz +7 more
TL;DR: Chemistries that Facilitate Nanotechnology Kim E. Sapsford,† W. Russ Algar, Lorenzo Berti, Kelly Boeneman Gemmill,‡ Brendan J. Casey,† Eunkeu Oh, Michael H. Stewart, and Igor L. Medintz .
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Nanochemistry and Nanomedicine for Nanoparticle-based Diagnostics and Therapy
TL;DR: This work presents a new generation of high-performance liquid chromatography platforms for selective separation of Na6(CO3) from Na4(SO4) through Na2SO4 and shows real-world applications in drug discovery and treatment of central nervous system disorders.
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Stimuli-responsive polymeric nanocarriers for the controlled transport of active compounds: Concepts and applications ☆
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Mesoporous Silica Nanoparticles for Intracellular Controlled Drug Delivery
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References
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Journal ArticleDOI
Nonviral gene delivery to the lung with copolymer-protected and transferrin-modified polyethylenimine
Carsten Rudolph,Ulrike Schillinger,Christian Plank,A. Gessner,P. Nicklaus,Rainer H. Müller,Joseph Rosenecker +6 more
TL;DR: Copolymers could be used to effectively shield polyplexes from interaction with components of the airway surface liquid (ASL) and increased gene delivery was found upon transferrin modification of the coated PEIpolyplexes suggesting a targeting effect.
Journal ArticleDOI
Gene Delivery Properties of End-Modified Poly(β-amino ester)s
Gregory T. Zugates,Nathan C. Tedford,Andreas Zumbuehl,Siddharth Jhunjhunwala,Christina S. Kang,Linda G. Griffith,Douglas A. Lauffenburger,Robert Langer,Daniel G. Anderson +8 more
TL;DR: It is shown that the terminal amine can greatly affect and improve polymer properties relevant to gene delivery and the optimal polymer:DNA ratio lowered 5-fold by conjugation of the appropriate end group.
Journal ArticleDOI
Monitoring DNA/poly-L-lysine polyplex formation with time-resolved multiangle laser light scattering.
Eva Lai,John H. van Zanten +1 more
TL;DR: The utility of TR-MALLS for monitoring the temporal evolution of DNA loading and supramolecular complex size growth (mean square radius and molar mass) throughout the DNA/poly-L-lysine polyplex formation process is demonstrated.
Journal ArticleDOI
A novel tetraester construct that reduces cationic lipid-associated cytotoxicity. Implications for the onset of cytotoxicity.
TL;DR: The present report is the first example of a linchpin tetraester construct that utilizes ester linkages to tether both the polar and hydrophobic domains and provided a significant lowering of cytotoxicity relative to DC-chol in the 16HBE14o- cells.
Journal ArticleDOI
Anti-JL1 antibody-conjugated poly (L-lysine) for targeted gene delivery to leukemia T cells.
TL;DR: DNA/antibody-PLL complexes were effectively internalized into Molt 4 cells after 4 h incubation at 37 degrees C and showed significantly higher in vitro transfection efficiency than DNA/PLL complex and DNA/Lipofectin formulation due to the targeting effect of receptor-mediated endocytosis induced by anti-JL1 antibody.