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
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Stimuli-responsive polymeric nanocarriers for the controlled transport of active compounds: Concepts and applications ☆
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References
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Journal ArticleDOI
Targeting tumors with non-viral gene delivery systems.
Manfred Ogris,Ernst Wagner +1 more
TL;DR: Tailor-made synthetic vectors can be used to achieve predominant gene expression in tumor tissue and, based on (poly)cationic carrier molecules, DNA can be efficiently targeted to tumors via the bloodstream.
Journal ArticleDOI
Effect of Polyethylene Glycol on Gene Delivery of Polyethylenimine
Shi-Joon Sung,Sang Hyun Min,Kuk Young Cho,Seongnam Lee,Younjin Min,Young Il Yeom,Jung-Ki Park +6 more
TL;DR: In the case of graft copolymers, the stability of polymer-DNA complexes and transfection efficiency were affected by the graft length and amount of PEG side chain, and the transfections efficiency was decreased.
Journal ArticleDOI
Decreased Binding to Proteins and Cells of Polymeric Gene Delivery Vectors Surface Modified with a Multivalent Hydrophilic Polymer and Retargeting through Attachment of Transferrin
Philip R. Dash,Martin L. Read,Kerry D. Fisher,Kenneth A. Howard,Margreet A. Wolfert,David Oupicky,Vladimir Subr,Jiri Strohalm,Karel Ulbrich,Leonard W. Seymour +9 more
TL;DR: The properties of these complexes, based on a multivalent reactive hydrophilic polymer, are promising candidates for targeted gene delivery, both in vitro and potentially in vivo.
Journal ArticleDOI
DNA-binding transferrin conjugates as functional gene-delivery agents: synthesis by linkage of polylysine or ethidium homodimer to the transferrin carbohydrate moiety
TL;DR: A more specific method for conjugation of transferrin with DNA-binding compounds involving attachment at the transferrin carbohydrate moiety is described, which facilitates the synthesis of large quantities (greater than 100 mg) of conjugates.
Journal ArticleDOI
Polyplexes assembled with internally quaternized PAMAM-OH dendrimer and plasmid DNA have a neutral surface and gene delivery potency.
Jung-Hoon Lee,Yong Beom Lim,Joon Sig Choi,Yan Lee,Tae-il Kim,Hyun-Jin Kim,Jae Keun Yoon,Kwan Kim,Jong-Sang Park +8 more
TL;DR: QPAMAM-OH showed much reduced cytotoxicity compared with starburst PAMAM and branched polyethyleneimine (PEI) in which shielding of interior positive charges by surface hydroxyls might be the reason for this favorable result.