Gene Transfer into the Lung by Nanoparticle Dextran-Spermine/Plasmid DNA Complexes

Abdullah, Saifollah; Yeo, Wendy Wai Yeng; Hosseinkhani, Hossein; Hosseinkhani, Mohsen; Masrawa, Ehab; Ramasamy, Rajesh; Rosli, Rozita; Rahman, Sabariah Abdul; Domb, Abraham J.

doi:10.1155/2010/284840

Cited by 44 publications

(33 citation statements)

References 56 publications

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“…We have reported that the dextran-spermine based polycations have been found to be highly effective as nonviral vectors in transfecting many different cells in vitro. [11][12][13][14][15][16][17] Our recent study also demonstrated that electrospun poly (glycolic acid) (PGA)/ collagen nanofibers significantly enhanced cell adhesion compared with PGA/collagen microfibers. 18 Based on these results, the present study aims to fabricate a tissue-like 3D transgene cell construct for use as a therapeutic cell-based gene delivery system or as an in vitro model system for testing genetic manipulations to understand the effects of gene expression on tissue development.…”

Section: Introductionmentioning

confidence: 99%

Development of 3D in vitro platform technology to engineer mesenchymal stem cells

Hosseinkhani¹,

Chen²,

Subramani³

et al. 2012

IJN

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This study aims to develop a three-dimensional in vitro culture system to genetically engineer mesenchymal stem cells (MSC) to express bone morphogenic protein-2. We employed nanofabrication technologies borrowed from the spinning industry, such as electrospinning, to mass-produce identical building blocks in a variety of shapes and sizes to fabricate electrospun nanofiber sheets comprised of composites of poly (glycolic acid) and collagen. Homogenous nanoparticles of cationic biodegradable natural polymer were formed by simple mixing of an aqueous solution of plasmid DNA encoded bone morphogenic protein-2 with the same volume of cationic polysaccharide, dextran-spermine. Rat bone marrow MSC were cultured on electrospun nanofiber sheets comprised of composites of poly (glycolic acid) and collagen prior to the incorporation of the nanoparticles into the nanofiber sheets. Bone morphogenic protein-2 was significantly detected in MSC cultured on nanofiber sheets incorporated with nanoparticles after 2 days compared with MSC cultured on nanofiber sheets incorporated with naked plasmid DNA. We conclude that the incorporation of nanoparticles into nanofiber sheets is a very promising strategy to genetically engineer MSC and can be used for further applications in regenerative medicine therapy.

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Section: Introductionmentioning

confidence: 99%

Development of 3D in vitro platform technology to engineer mesenchymal stem cells

Hosseinkhani¹,

Chen²,

Subramani³

et al. 2012

IJN

Self Cite

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“…Dextran is neutral at physiological pH and therefore does not effectively bind DNA, thus cationic molecules or polymers are commonly incorporated into dextran NPs to improve their effectiveness in gene therapy applications. Dextran NPs incorporating cationic methacrylate monomers and spermine (a tetravalent amine) have been used for the delivery of plasmid DNA in vitro (COS7 and HEK293) and in vivo (trachea and lung, and colorectal cancer) [157–159]. Other dextran NPs conjugated to cationic polymers such as PEI or poly-β-amino ester also show high binding efficiency to plasmid DNA, as well as the ability to escape endosomes [160, 161].…”

Section: Nps For Retinal Gene Therapymentioning

confidence: 99%

Nanoparticle-based technologies for retinal gene therapy

Adijanto

Naash

2015

European Journal of Pharmaceutics and Biopharmaceutics

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For patients with hereditary retinal diseases, retinal gene therapy offers significant promise for the prevention of retinal degeneration. While adeno-associated virus (AAV)-based systems remain the most popular gene delivery method due to their high efficiency and successful clinical results, other delivery systems, such as non-viral nanoparticles (NPs) are being developed as additional therapeutic options. NP technologies come in several categories (e.g., polymer, liposomes, peptide compacted DNA), several of which have been tested in mouse models of retinal disease. Here, we discuss the key biochemical features of the different NPs that influence how they are internalized into cells, escape from endosomes, and are delivered into the nucleus. We review the primary mechanism of NP uptake by retinal cells and highlight various NPs that have been successfully used for in vivo gene delivery to the retina and RPE. Finally, we consider the various strategies that can be implemented in the plasmid DNA to generate persistent, high levels of gene expression.

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“…A novel cationic polymer, dextran-spermine, has been found to mediate gene expression in a wide variety of cell lines and in vivo through systemic delivery of plasmid DNA, partially protected from degradation by nuclease. This exhibited optimal gene transfer effi ciency [ 41 ].…”

Section: Dextranmentioning

confidence: 99%