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Dendrons with spermine surface groups as potential building blocks for nonviral vectors in gene therapy

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Dendrons with spermine surface groups as potential building blocks for nonviral vectors in gene therapy. / Hardy, John G.; Kostiainen, Mauri A.; Smith, David K.; Gabrielson, Nathan P.; Pack, Daniel W.

In: Bioconjugate Chemistry, Vol. 17, No. 1, 04.11.2006, p. 172-178.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Hardy, JG, Kostiainen, MA, Smith, DK, Gabrielson, NP & Pack, DW 2006, 'Dendrons with spermine surface groups as potential building blocks for nonviral vectors in gene therapy', Bioconjugate Chemistry, vol. 17, no. 1, pp. 172-178. https://doi.org/10.1021/bc050212r

APA

Hardy, J. G., Kostiainen, M. A., Smith, D. K., Gabrielson, N. P., & Pack, D. W. (2006). Dendrons with spermine surface groups as potential building blocks for nonviral vectors in gene therapy. Bioconjugate Chemistry, 17(1), 172-178. https://doi.org/10.1021/bc050212r

Vancouver

Hardy JG, Kostiainen MA, Smith DK, Gabrielson NP, Pack DW. Dendrons with spermine surface groups as potential building blocks for nonviral vectors in gene therapy. Bioconjugate Chemistry. 2006 Nov 4;17(1):172-178. https://doi.org/10.1021/bc050212r

Author

Hardy, John G. ; Kostiainen, Mauri A. ; Smith, David K. ; Gabrielson, Nathan P. ; Pack, Daniel W. / Dendrons with spermine surface groups as potential building blocks for nonviral vectors in gene therapy. In: Bioconjugate Chemistry. 2006 ; Vol. 17, No. 1. pp. 172-178.

Bibtex

@article{6006080c88ac48ec8032bc1aa21c4000,
title = "Dendrons with spermine surface groups as potential building blocks for nonviral vectors in gene therapy",
abstract = "This paper investigates a series of dendrons based on the Newkome dendritic scaffold that displays a naturally occurring polyamine (spermine) on their surface. These dendrons have previously been shown to interact with DNA in a generation dependent manner with the more highly branched dendrons exhibiting a strong multivalency effect for the spermine surface groups. In this paper, we investigate the ability of these dendrons to transfect DNA into cells (human breast carcinoma cells, MDA-MB-231, and murine myoblast cells, C2C12) as determined by the luciferase assay. Although the dendrons are unable to transfect DNA in their own right, they are capable of delivering DNA in vitro when administered with chloroquine, which assists with escape from endocytic vesicles. The cytotoxicity of the dendrons was determined using the XTT assay, and it was shown that the dendrons were nontoxic either alone or in the presence of DNA. However, when administered with DNA and chloroquine, the most highly branched dendron did exhibit some cytotoxicity. This paper elucidates the relationship between in vitro transfection efficiency and toxicity. While transfection efficiencies are modest, the low toxicity of the dendrons, both in their own right, and in the presence of DNA, provides encouragement that this type of building block, which has a relatively high affinity for DNA, will provide a useful starting point for the further synthetic development of more effective gene transfection agents.",
keywords = "CATIONIC GEMINI SURFACTANTS, IN-VITRO, POLYAMIDOAMINE DENDRIMERS, CASCADE POLYMERS, CYSTIC-FIBROSIS, PLASMID DNA, GLYCOL)-BLOCK-POLY(L-LYSINE) DENDRIMER, DELIVERY, TRANSFECTION, CANCER, Gene Transfer Techniques, non-viral vectors, gene delivery, gene therapy, Chemistry(all), Biomaterials",
author = "Hardy, {John G.} and Kostiainen, {Mauri A.} and Smith, {David K.} and Gabrielson, {Nathan P.} and Pack, {Daniel W.}",
year = "2006",
month = nov,
day = "4",
doi = "10.1021/bc050212r",
language = "English",
volume = "17",
pages = "172--178",
journal = "Bioconjugate Chemistry",
issn = "1043-1802",
publisher = "American Chemical Society",
number = "1",

}

RIS

TY - JOUR

T1 - Dendrons with spermine surface groups as potential building blocks for nonviral vectors in gene therapy

AU - Hardy, John G.

AU - Kostiainen, Mauri A.

AU - Smith, David K.

AU - Gabrielson, Nathan P.

AU - Pack, Daniel W.

PY - 2006/11/4

Y1 - 2006/11/4

N2 - This paper investigates a series of dendrons based on the Newkome dendritic scaffold that displays a naturally occurring polyamine (spermine) on their surface. These dendrons have previously been shown to interact with DNA in a generation dependent manner with the more highly branched dendrons exhibiting a strong multivalency effect for the spermine surface groups. In this paper, we investigate the ability of these dendrons to transfect DNA into cells (human breast carcinoma cells, MDA-MB-231, and murine myoblast cells, C2C12) as determined by the luciferase assay. Although the dendrons are unable to transfect DNA in their own right, they are capable of delivering DNA in vitro when administered with chloroquine, which assists with escape from endocytic vesicles. The cytotoxicity of the dendrons was determined using the XTT assay, and it was shown that the dendrons were nontoxic either alone or in the presence of DNA. However, when administered with DNA and chloroquine, the most highly branched dendron did exhibit some cytotoxicity. This paper elucidates the relationship between in vitro transfection efficiency and toxicity. While transfection efficiencies are modest, the low toxicity of the dendrons, both in their own right, and in the presence of DNA, provides encouragement that this type of building block, which has a relatively high affinity for DNA, will provide a useful starting point for the further synthetic development of more effective gene transfection agents.

AB - This paper investigates a series of dendrons based on the Newkome dendritic scaffold that displays a naturally occurring polyamine (spermine) on their surface. These dendrons have previously been shown to interact with DNA in a generation dependent manner with the more highly branched dendrons exhibiting a strong multivalency effect for the spermine surface groups. In this paper, we investigate the ability of these dendrons to transfect DNA into cells (human breast carcinoma cells, MDA-MB-231, and murine myoblast cells, C2C12) as determined by the luciferase assay. Although the dendrons are unable to transfect DNA in their own right, they are capable of delivering DNA in vitro when administered with chloroquine, which assists with escape from endocytic vesicles. The cytotoxicity of the dendrons was determined using the XTT assay, and it was shown that the dendrons were nontoxic either alone or in the presence of DNA. However, when administered with DNA and chloroquine, the most highly branched dendron did exhibit some cytotoxicity. This paper elucidates the relationship between in vitro transfection efficiency and toxicity. While transfection efficiencies are modest, the low toxicity of the dendrons, both in their own right, and in the presence of DNA, provides encouragement that this type of building block, which has a relatively high affinity for DNA, will provide a useful starting point for the further synthetic development of more effective gene transfection agents.

KW - CATIONIC GEMINI SURFACTANTS

KW - IN-VITRO

KW - POLYAMIDOAMINE DENDRIMERS

KW - CASCADE POLYMERS

KW - CYSTIC-FIBROSIS

KW - PLASMID DNA

KW - GLYCOL)-BLOCK-POLY(L-LYSINE) DENDRIMER

KW - DELIVERY

KW - TRANSFECTION

KW - CANCER

KW - Gene Transfer Techniques

KW - non-viral vectors

KW - gene delivery

KW - gene therapy

KW - Chemistry(all)

KW - Biomaterials

U2 - 10.1021/bc050212r

DO - 10.1021/bc050212r

M3 - Journal article

VL - 17

SP - 172

EP - 178

JO - Bioconjugate Chemistry

JF - Bioconjugate Chemistry

SN - 1043-1802

IS - 1

ER -