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
Gene delivery into mesenchymal stem cells: a biomimetic approach using RGD nanoclusters based on poly(amidoamine) dendrimers.
Deepti Pandita,José Luís Guedes dos Santos,João Rodrigues,Ana Paula Pêgo,Pedro L. Granja,Helena Tomás +5 more
TL;DR: The use of dendrimer scaffolds for RGD cluster formation is a new approach that can be extended beyond gene delivery applications, whenever RGD clustering is important for modulating cellular responses.
Journal ArticleDOI
Synthetic Polymer Nanoparticle–Polysaccharide Interactions: A Systematic Study
Zhiyang Zeng,Jiten Patel,Shih-Hui Lee,Monica E. McCallum,Anuradha Tyagi,Mingdi Yan,Kenneth J. Shea +6 more
TL;DR: A systematic investigation of the interaction between synthetic polymer nanoparticles and polysaccharides is reported by ITC, SPR, and an anticoagulant assay to provide guidelines to engineer nanoparticles for biomedical applications and finds that high charge density and cross-linking of the NP can contribute to high affinity.
Journal ArticleDOI
Effect of polymer structure on micelles formed between siRNA and cationic block copolymer comprising thiols and amidines
R. James Christie,Kanjiro Miyata,Yu Matsumoto,Yu Matsumoto,Takahiro Nomoto,Daniel Menasco,Tsz Chung Lai,Matthew Pennisi,Kensuke Osada,Shigeto Fukushima,Nobuhiro Nishiyama,Yuichi Yamasaki,Kazunori Kataoka +12 more
TL;DR: The properties of micellar siRNA delivery vehicles prepared with poly(ethylene glycol)-block-poly(l-lysine) (PEG-b-PLL) comprising lysine amines modified to contain amidine and thiol functionality are investigated, which affected micelle formation behavior and stability along with in vitro and in vivo performance.
Journal ArticleDOI
Silica nanoparticle supported lipid bilayers for gene delivery
TL;DR: Silica nanoparticle supported cationic lipids can effectively bind plasmid DNAs and transfect mammalian cells with an efficiency that depends on both the particle size and lipid composition; here the gene delivery and expression process has been confirmed by confocal fluorescence microscopy.
Journal ArticleDOI
Enhancement of magnetic nanoparticle-mediated gene transfer to astrocytes by 'magnetofection': effects of static and oscillating fields.
Mark R. Pickard,Divya M. Chari +1 more
TL;DR: MNP vectors can safely and effectively transfect rodent astrocytes and could form the basis of a 'multifunctional nanoplatform' for neural cell transplantation.
References
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Journal ArticleDOI
A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: polyethylenimine
Otmane Boussif,Frank Lezoualc'h,Maria Antonietta Zanta,Mojgan Mergny,Daniel Scherman,Barbara A. Demeneix,Jean-Paul Behr +6 more
TL;DR: Together, these properties make PEI a promising vector for gene therapy and an outstanding core for the design of more sophisticated devices because its efficiency relies on extensive lysosome buffering that protects DNA from nuclease degradation, and consequent lysOSomal swelling and rupture that provide an escape mechanism for the PEI/DNA particles.
Journal ArticleDOI
Lipofection: a highly efficient, lipid-mediated DNA-transfection procedure
Philip L. Felgner,Thomas R. Gadek,Marilyn Holm,Richard Bolton Roman,Hardy W. Chan,Michael Wenz,Jeffrey P. Northrop,Gordon M. Ringold,Mark Danielsen +8 more
TL;DR: Depending upon the cell line, lipofection is from 5- to greater than 100-fold more effective than either the calcium phosphate or the DEAE-dextran transfection technique.
Journal ArticleDOI
Direct gene transfer into mouse muscle in vivo.
Jon A. Wolff,Robert W. Malone,Phillip Williams,Wang Chong,Gyula Acsadi,Agnes Jani,Philip L. Felgner +6 more
TL;DR: RNA and DNA expression vectors containing genes for chloramphenicol acetyltransferase, luciferase, and beta-galactosidase were separately injected into mouse skeletal muscle in vivo and expression was comparable to that obtained from fibroblasts transfected in vitro under optimal conditions.
Journal ArticleDOI
A new class of polymers: Starburst-dendritic macromolecules
Donald A. Tomalia,H. Baker,James R Dewald,Michael B. Hall,G. Kallos,Steven J. Martin,J. Roeck,J. Ryder,Patrick B. Smith +8 more
TL;DR: Starburst polymers as mentioned in this paper are a class of topological macromolecules which are derived from classical monomers/oligomers by their extraordinary symmetry, high branching and maximized terminal functionality density.