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
Dynamic Self-Assembly of Polycationic Clusters Based on Cyclodextrins for pH-Sensitive DNA Nanocondensation and Delivery by Component Design
Laura Gallego-Yerga,M. José González-Álvarez,Natalia Mayordomo,Francisco Santoyo-Gonzalez,Juan M. Benito,Carmen Ortiz Mellet,Francisco Mendicuti,José M. García Fernández +7 more
TL;DR: The ability of cyclodextrin-based polycationic cluster to undergo reversible DNA condensation and release in a physiologically useful pH window has been finely tuned by the installation of a capping xylylene moiety at the secondary face of the cyclooligosaccharide.
Journal ArticleDOI
Increase in transgene expression by pluronic L64-mediated endosomal/lysosomal escape through its membrane-disturbing action
TL;DR: When applied properly, Pluronic L64 not only significantly increased polyethylenimine- and liposome-mediated transgene expression, but also decreased the cytotoxicity occasioned by transfection process.
Journal ArticleDOI
Assembly of polyethylenimine-functionalized iron oxide nanoparticles as agents for DNA transfection with magnetofection technique.
TL;DR: Different methods for PEI immobilization on smaller MNPs were adopted to compare DNA binding abilities, transfection and transient gene expression efficiencies, and the mechanism of DNA magnetofection was studied.
Journal ArticleDOI
In situ dual-crosslinked nanoparticles for tumor targeting gene delivery
TL;DR: In this study, a facile fabrication platform is constructed to endow the gene delivery system with high stability in the circulation system and achieve targeted delivery of plasmid DNA (pDNA) into cancer cells.
Journal ArticleDOI
Degradable gene delivery systems based on Pluronics-modified low-molecular-weight polyethylenimine: preparation, characterization, intracellular trafficking, and cellular distribution
Wei Fan,Xin Wu,Baoyue Ding,Jing Gao,Zhen Cai,Wei Zhang,Dongfeng Yin,Xiang Wang,Quangang Zhu,Jiyong Liu,Xueying Ding,Shen Gao +11 more
TL;DR: A series of cationic copolymers obtained by grafting polyethyleneimine with nonionic amphiphilic surfactant polyether-Pluronic consisting of hydrophilic ethylene oxide and hydrophobic propylene oxide blocks are synthesized and characterized.
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.