Polyplexes and Lipoplexes for mammalian gene delivery: from traditional to Microarray screening

Gene therapy requires the development of non-toxic and highly efficient delivery systems for DNA and RNAi. Polycations, especially dendrimers, have shown enormous potential as gene transfer vehicles, displaying minimal toxicity with a broad range of cell lines. In this paper, a total of 13 dendrimer...

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Main Authors: How, Siew Eng, Boon-ek Yingyongnarongkul, Fara, M. A., Juan J Diaz-Mochon, Mittoo, S., Mark Bradley
Format: Article
Language:English
Published: 2004
Subjects:
Online Access:https://eprints.ums.edu.my/id/eprint/19309/1/Polyplexes%20and%20Lipoplexes%20for%20mammalian%20gene%20delivery.pdf
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author How, Siew Eng
Boon-ek Yingyongnarongkul
Fara, M. A.
Juan J Diaz-Mochon
Mittoo, S.
Mark Bradley
author_facet How, Siew Eng
Boon-ek Yingyongnarongkul
Fara, M. A.
Juan J Diaz-Mochon
Mittoo, S.
Mark Bradley
author_sort How, Siew Eng
collection UMS
description Gene therapy requires the development of non-toxic and highly efficient delivery systems for DNA and RNAi. Polycations, especially dendrimers, have shown enormous potential as gene transfer vehicles, displaying minimal toxicity with a broad range of cell lines. In this paper, a total of 13 dendrimers, up to G3.0, were constructed from AB3 type isocyanate monomers using solid phase methodology and evaluated for transfection activity. Among the library of compounds prepared, a G3.0 dendrimer displayed comparable activity to Superfect. Gel retardation assays demonstrated that all of the compounds completely bound plasmid DNA, indicating the efficient formation of complexes between DNA and the dendrimers. A “transfection microarray” approach was developed for screening these compounds as well as a panel of lipoplexes (complexes of DNA with cationic lipids) and polyplexes (complexes of DNA with synthetic polycationic polymers), in 3D solution like micro-assay). Five cationic lipids with a cholesterol tail showed stronger or comparable transfection activity relative to Effectene. The new, micro-array screening method was rapid and miniaturized, offering the potential of high throughput screening of large libraries of transfection candidates, with thousands of library members per array, and the ability to rapidly screen a broad range of cell types.
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spelling ums.eprints-193092018-03-15T02:03:42Z https://eprints.ums.edu.my/id/eprint/19309/ Polyplexes and Lipoplexes for mammalian gene delivery: from traditional to Microarray screening How, Siew Eng Boon-ek Yingyongnarongkul Fara, M. A. Juan J Diaz-Mochon Mittoo, S. Mark Bradley QP Physiology Gene therapy requires the development of non-toxic and highly efficient delivery systems for DNA and RNAi. Polycations, especially dendrimers, have shown enormous potential as gene transfer vehicles, displaying minimal toxicity with a broad range of cell lines. In this paper, a total of 13 dendrimers, up to G3.0, were constructed from AB3 type isocyanate monomers using solid phase methodology and evaluated for transfection activity. Among the library of compounds prepared, a G3.0 dendrimer displayed comparable activity to Superfect. Gel retardation assays demonstrated that all of the compounds completely bound plasmid DNA, indicating the efficient formation of complexes between DNA and the dendrimers. A “transfection microarray” approach was developed for screening these compounds as well as a panel of lipoplexes (complexes of DNA with cationic lipids) and polyplexes (complexes of DNA with synthetic polycationic polymers), in 3D solution like micro-assay). Five cationic lipids with a cholesterol tail showed stronger or comparable transfection activity relative to Effectene. The new, micro-array screening method was rapid and miniaturized, offering the potential of high throughput screening of large libraries of transfection candidates, with thousands of library members per array, and the ability to rapidly screen a broad range of cell types. 2004 Article PeerReviewed text en https://eprints.ums.edu.my/id/eprint/19309/1/Polyplexes%20and%20Lipoplexes%20for%20mammalian%20gene%20delivery.pdf How, Siew Eng and Boon-ek Yingyongnarongkul and Fara, M. A. and Juan J Diaz-Mochon and Mittoo, S. and Mark Bradley (2004) Polyplexes and Lipoplexes for mammalian gene delivery: from traditional to Microarray screening. Combinatorial Chemistry and High Throughput Screening, 7 (5). pp. 423-430. http://dx.doi.org/10.2174/1386207043328616
spellingShingle QP Physiology
How, Siew Eng
Boon-ek Yingyongnarongkul
Fara, M. A.
Juan J Diaz-Mochon
Mittoo, S.
Mark Bradley
Polyplexes and Lipoplexes for mammalian gene delivery: from traditional to Microarray screening
title Polyplexes and Lipoplexes for mammalian gene delivery: from traditional to Microarray screening
title_full Polyplexes and Lipoplexes for mammalian gene delivery: from traditional to Microarray screening
title_fullStr Polyplexes and Lipoplexes for mammalian gene delivery: from traditional to Microarray screening
title_full_unstemmed Polyplexes and Lipoplexes for mammalian gene delivery: from traditional to Microarray screening
title_short Polyplexes and Lipoplexes for mammalian gene delivery: from traditional to Microarray screening
title_sort polyplexes and lipoplexes for mammalian gene delivery from traditional to microarray screening
topic QP Physiology
url https://eprints.ums.edu.my/id/eprint/19309/1/Polyplexes%20and%20Lipoplexes%20for%20mammalian%20gene%20delivery.pdf
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