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
More filters
Journal ArticleDOI
Additive nanocomplexes of cationic lipopolymers for improved non-viral gene delivery to mesenchymal stem cells
TL;DR: It is concluded that PEI-tLA of low lipid substitution can be employed as a gene carrier to design supersensitive nano-formulations and was comparable to or higher than commercial transfection reagents.
Journal ArticleDOI
Lectin functionalized nanocarriers for gene delivery.
Virendra Gajbhiye,Shaoqin Gong +1 more
TL;DR: Light is shed on various gene delivery nanovectors conjugated with either lectins or carbohydrates for enhanced gene transfection through either direct or reverse lectin targeting strategies.
Journal ArticleDOI
Galactose‐Functionalized Cationic Polycarbonate Diblock Copolymer for Targeted Gene Delivery to Hepatocytes
TL;DR: The galactose-functionalized cationic polycarbonate diblock copolymer has potential for use as a non-viral gene vector for the targeted delivery of therapeutic genes to hepatocytes in the treatment of liver diseases.
Patent
Biodegradable lipids for delivery of nucleic acids
Derosa Frank,Heartlein Michael +1 more
TL;DR: In this article, a biodegradable compound of formula I, and sub-formulas thereof: Formula (I) or a pharmaceutically acceptable salt thereof, where each X independently is O or S, each Y independently is N, and each R 1 independently is defined.
Journal ArticleDOI
Cationic nucleolipids as efficient siRNA carriers
TL;DR: Five novel uridine-based cationic nucleolipids are synthesized, introducing basic amino acid residues at the 5' position of uridine, through 1,3-dipolar cycloaddition, and hydrophobic alkyl moieties at the 2' and 3' positions, through carbamate linkages.
References
More filters
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.