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Journal ArticleDOI

Nonviral Vectors for Gene Delivery

Meredith A. Mintzer, +1 more
- 01 Feb 2009 - 
- Vol. 109, Iss: 2, pp 259-302
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 less

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Citations
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Antibody-Linked Spherical Nucleic Acids for Cellular Targeting

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Nanomedicines for cancer therapy: state-of-the-art and limitations to pre-clinical studies that hinder future developments.

TL;DR: It is shown how the lack of uniformity in preclinical trials prevents systematic comparison and hence limits advances in the field, allowing new approaches for reducing the unwanted side effects of systemic delivery, increasing tumor accumulation, and improving efficacy.
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Functional lipids and lipoplexes for improved gene delivery.

TL;DR: This manuscript reviews recent advances in pH, redox, and charge-reversal sensitive lipids and suggests avenues for further research into nucleic acid-lipid interactions.
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Revisit complexation between DNA and polyethylenimine--effect of length of free polycationic chains on gene transfection.

TL;DR: The result shows that the "proton sponge" effect is not dominant because the shut-down of the proton pump only partially attenuates the transfection efficiency, and the cellular uptake kinetics studied by flow cytometry reveals that long free chains increase the uptake rate constant of the DNA/PEI complexes.
References
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Journal ArticleDOI

A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: polyethylenimine

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

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.

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

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.
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