Augmentation of myocardial transfection using TerplexDNA: A novel gene delivery system

D. G. Affleck; L. Yu; D. A. Bull; S. H. Bailey; S. W. Kim

doi:10.1038/sj.gt.3301395

Augmentation of myocardial transfection using TerplexDNA: A novel gene delivery system

D. G. Affleck, L. Yu, D. A. Bull, S. H. Bailey, S. W. Kim

Research output: Contribution to journal › Article › peer-review

52 Scopus citations

Abstract

Gene therapy is a potential new strategy for the treatment of cardiovascular disease. The most efficacious method of gene delivery remains a key hurdle to effective gene therapy. We present the application of a novel, nonviral gene delivery system (TerplexDNA) to augment myocardial transfection. The hearts of New Zealand white rabbits were injected with reporter genes, luciferase cDNA or β-galactosidase cDNA, either as naked plasmid DNA or plasmid DNA complexed with stearyl-poly(L-lysine)-low density lipoprotein (TerplexDNA). Three day left heart myocardial cell lysates produced 44571 ± 8730 RLU (RLU = total light units/mg protein) for the TerplexDNA luciferase rabbits versus 1638 ± 567 RLU for the naked luciferase rabbits (P = 0.002). Thirty days after injection, myocardial lysates produced 677 ± 52 RLU for the TerplexDNA luciferase hearts versus 18 ± 3 RLU for the naked luciferase hearts (P = 0.002). Histologic analysis of the hearts transfected with β-galactosidade showed that TerplexDNA increased the area and depth of transfection compared with the naked plasmid DNA alone. The hearts of Sprague-Dawley rats were injected in a similar fashion and analyzed at 1, 3, 5, 10, 15, 25 and 30 days after injection. The naked luciferase injected hearts showed transient elevation of luciferase activity to day 5 but fell back to baseline levels after that time-point. The TerplexDNA luciferase injected hearts had significantly elevated luciferase activity to 30 days. The Terplex gene delivery system significantly augments myocardial transfection compared with a naked plasmid DNA system alone. The advantage in transfection efficiency appears to be related to the unique properties of the TerplexDNA carrier molecule. The TerplexDNA delivery system represents a novel means to augment transfection of the myocardium.

Original language	English (US)
Pages (from-to)	349-353
Number of pages	5
Journal	Gene Therapy
Volume	8
Issue number	5
DOIs	https://doi.org/10.1038/sj.gt.3301395
State	Published - 2001
Externally published	Yes

Keywords

Direct injection
Gene delivery
Myocardium
TerplexDNA
Transfection

ASJC Scopus subject areas

Molecular Medicine
Molecular Biology
Genetics

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10.1038/sj.gt.3301395

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title = "Augmentation of myocardial transfection using TerplexDNA: A novel gene delivery system",

abstract = "Gene therapy is a potential new strategy for the treatment of cardiovascular disease. The most efficacious method of gene delivery remains a key hurdle to effective gene therapy. We present the application of a novel, nonviral gene delivery system (TerplexDNA) to augment myocardial transfection. The hearts of New Zealand white rabbits were injected with reporter genes, luciferase cDNA or β-galactosidase cDNA, either as naked plasmid DNA or plasmid DNA complexed with stearyl-poly(L-lysine)-low density lipoprotein (TerplexDNA). Three day left heart myocardial cell lysates produced 44571 ± 8730 RLU (RLU = total light units/mg protein) for the TerplexDNA luciferase rabbits versus 1638 ± 567 RLU for the naked luciferase rabbits (P = 0.002). Thirty days after injection, myocardial lysates produced 677 ± 52 RLU for the TerplexDNA luciferase hearts versus 18 ± 3 RLU for the naked luciferase hearts (P = 0.002). Histologic analysis of the hearts transfected with β-galactosidade showed that TerplexDNA increased the area and depth of transfection compared with the naked plasmid DNA alone. The hearts of Sprague-Dawley rats were injected in a similar fashion and analyzed at 1, 3, 5, 10, 15, 25 and 30 days after injection. The naked luciferase injected hearts showed transient elevation of luciferase activity to day 5 but fell back to baseline levels after that time-point. The TerplexDNA luciferase injected hearts had significantly elevated luciferase activity to 30 days. The Terplex gene delivery system significantly augments myocardial transfection compared with a naked plasmid DNA system alone. The advantage in transfection efficiency appears to be related to the unique properties of the TerplexDNA carrier molecule. The TerplexDNA delivery system represents a novel means to augment transfection of the myocardium.",

keywords = "Direct injection, Gene delivery, Myocardium, TerplexDNA, Transfection",

author = "Affleck, {D. G.} and L. Yu and Bull, {D. A.} and Bailey, {S. H.} and Kim, {S. W.}",

note = "Funding Information: This work was supported by Expression Genetics Inc, and the NIH Grant (RO1, HL65477–01), Functional and Targeting Polymeric Gene Carrier. Special thanks to Elizabeth Hammond MD for her gracious help with histologic preparation and evaluation and to Qifu Wang for her technical support.",

year = "2001",

doi = "10.1038/sj.gt.3301395",

language = "English (US)",

volume = "8",

pages = "349--353",

journal = "Gene Therapy",

issn = "0969-7128",

publisher = "Springer Nature",

number = "5",

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TY - JOUR

T1 - Augmentation of myocardial transfection using TerplexDNA

T2 - A novel gene delivery system

AU - Affleck, D. G.

AU - Yu, L.

AU - Bull, D. A.

AU - Bailey, S. H.

AU - Kim, S. W.

N1 - Funding Information: This work was supported by Expression Genetics Inc, and the NIH Grant (RO1, HL65477–01), Functional and Targeting Polymeric Gene Carrier. Special thanks to Elizabeth Hammond MD for her gracious help with histologic preparation and evaluation and to Qifu Wang for her technical support.

PY - 2001

Y1 - 2001

N2 - Gene therapy is a potential new strategy for the treatment of cardiovascular disease. The most efficacious method of gene delivery remains a key hurdle to effective gene therapy. We present the application of a novel, nonviral gene delivery system (TerplexDNA) to augment myocardial transfection. The hearts of New Zealand white rabbits were injected with reporter genes, luciferase cDNA or β-galactosidase cDNA, either as naked plasmid DNA or plasmid DNA complexed with stearyl-poly(L-lysine)-low density lipoprotein (TerplexDNA). Three day left heart myocardial cell lysates produced 44571 ± 8730 RLU (RLU = total light units/mg protein) for the TerplexDNA luciferase rabbits versus 1638 ± 567 RLU for the naked luciferase rabbits (P = 0.002). Thirty days after injection, myocardial lysates produced 677 ± 52 RLU for the TerplexDNA luciferase hearts versus 18 ± 3 RLU for the naked luciferase hearts (P = 0.002). Histologic analysis of the hearts transfected with β-galactosidade showed that TerplexDNA increased the area and depth of transfection compared with the naked plasmid DNA alone. The hearts of Sprague-Dawley rats were injected in a similar fashion and analyzed at 1, 3, 5, 10, 15, 25 and 30 days after injection. The naked luciferase injected hearts showed transient elevation of luciferase activity to day 5 but fell back to baseline levels after that time-point. The TerplexDNA luciferase injected hearts had significantly elevated luciferase activity to 30 days. The Terplex gene delivery system significantly augments myocardial transfection compared with a naked plasmid DNA system alone. The advantage in transfection efficiency appears to be related to the unique properties of the TerplexDNA carrier molecule. The TerplexDNA delivery system represents a novel means to augment transfection of the myocardium.

AB - Gene therapy is a potential new strategy for the treatment of cardiovascular disease. The most efficacious method of gene delivery remains a key hurdle to effective gene therapy. We present the application of a novel, nonviral gene delivery system (TerplexDNA) to augment myocardial transfection. The hearts of New Zealand white rabbits were injected with reporter genes, luciferase cDNA or β-galactosidase cDNA, either as naked plasmid DNA or plasmid DNA complexed with stearyl-poly(L-lysine)-low density lipoprotein (TerplexDNA). Three day left heart myocardial cell lysates produced 44571 ± 8730 RLU (RLU = total light units/mg protein) for the TerplexDNA luciferase rabbits versus 1638 ± 567 RLU for the naked luciferase rabbits (P = 0.002). Thirty days after injection, myocardial lysates produced 677 ± 52 RLU for the TerplexDNA luciferase hearts versus 18 ± 3 RLU for the naked luciferase hearts (P = 0.002). Histologic analysis of the hearts transfected with β-galactosidade showed that TerplexDNA increased the area and depth of transfection compared with the naked plasmid DNA alone. The hearts of Sprague-Dawley rats were injected in a similar fashion and analyzed at 1, 3, 5, 10, 15, 25 and 30 days after injection. The naked luciferase injected hearts showed transient elevation of luciferase activity to day 5 but fell back to baseline levels after that time-point. The TerplexDNA luciferase injected hearts had significantly elevated luciferase activity to 30 days. The Terplex gene delivery system significantly augments myocardial transfection compared with a naked plasmid DNA system alone. The advantage in transfection efficiency appears to be related to the unique properties of the TerplexDNA carrier molecule. The TerplexDNA delivery system represents a novel means to augment transfection of the myocardium.

KW - Direct injection

KW - Gene delivery

KW - Myocardium

KW - TerplexDNA

KW - Transfection

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U2 - 10.1038/sj.gt.3301395

DO - 10.1038/sj.gt.3301395

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SN - 0969-7128

VL - 8

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JO - Gene Therapy

JF - Gene Therapy

IS - 5

ER -

Augmentation of myocardial transfection using TerplexDNA: A novel gene delivery system

Abstract

Keywords

ASJC Scopus subject areas

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