Hydrodynamics-based gene delivery of naked DNA encoding fetal liver kinase-1 gene effectively suppresses the growth of pre-existing tumors.

Hydrodynamics-based gene delivery of naked DNA encoding fetal liver kinase-1 gene effectively suppresses the growth of pre-existing tumors. Research Abstract Details 

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Hydrodynamics-based gene delivery of naked DNA encoding fetal liver kinase-1 gene effectively suppresses the growth of pre-existing tumors. Abstract Text:

H Yazawa,T Murakami,H-M Li,T Back,K Kurosaka,Y Suzuki,L Shorts,Y Akiyama,K Maruyama,E Parsoneault,R H Wiltrout,M Watanabe,

Antiangiogenic gene therapy is a promising strategy for cancer treatment, which generally requires highly efficient delivery systems. To date, success of this strategy has depended almost exclusively on the delivery of high titers of viral vectors, which can result in effective transgene expression. However, their cytotoxicity and immunogenicity are a major concern for clinical applications. Recent advances in delivery efficiency of naked DNA could potentially meet the requirement for both high transgene expression and minimal side effects. To investigate whether naked DNA can be used for antiangiogenic cancer therapy, an expression plasmid was generated that encodes a soluble form of fetal liver kinase-1 (Flk-1) gene, a receptor for vascular endothelial growth factor (VEGF). Hydrodynamic injection of this plasmid resulted in close to 0.1 mg/ml of soluble Flk-1 protein in mouse serum and blocked VEGF-driven angiogenesis in matrigel in vivo. The same delivery significantly suppressed the growth of two different pre-existing subcutaneous tumors, Renca renal cell carcinoma and 3LL lung carcinoma. CD31 immunohistochemistry revealed that the tumor-associated angiogenesis was also highly attenuated in soluble Flk-1-treated mice. Thus, expression of genes by hydrodynamics-based gene delivery of naked DNA appears to be a promising approach for antiangiogenic cancer gene therapy.

Hydrodynamics-based gene delivery of naked DNA encoding fetal liver kinase-1 gene effectively suppresses the growth of pre-existing tumors. Publishing Authors By Initials

H Yazawa,T Murakami,HM Li,T Back,K Kurosaka,Y Suzuki,L Shorts,Y Akiyama,K Maruyama,E Parsoneault,RH Wiltrout,M Watanabe,

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Hydrodynamics-based gene delivery of naked DNA encoding fetal liver kinase-1 gene effectively suppresses the growth of pre-existing tumors. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Cancer gene therapy

VOLUME: 13

Page Numbers: 993-1001

Journal Abbreviation: Cancer Gene Ther.

ISSN: 0929-1903

DAY: 9

MONTH: 06

YEAR: 2006

Hydrodynamics-based gene delivery of naked DNA encoding fetal liver kinase-1 gene effectively suppresses the growth of pre-existing tumors. Information

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LANGUAGE: eng

NlmUniqueID: 9432230

Hydrodynamics-based gene delivery of naked DNA encoding fetal liver kinase-1 gene effectively suppresses the growth of pre-existing tumors. Keywords Mesh Terms:

KEYWORDS: Vascular Endothelial Growth Factor Recep

MESH TERMS: genetics

Chemical & Substance for Abstract: Hydrodynamics-based gene delivery of naked DNA encoding fetal liver kinase-1 gene effectively suppresses the growth of pre-existing tumors. Information

Substance Name: Vascular Endothelial Growth Factor Recep

Registry Number: EC 2.7.1.112

Grant and Affiliation Information for Hydrodynamics-based gene delivery of naked DNA encoding fetal liver kinase-1 gene effectively suppresses the growth of pre-existing tumors.

AFFILIATION: Laboratory of Experimental Immunology, NCI Center for Cancer Research, Frederick, MD 21702, USA.

Country: England

AGENCY: United States NCI

GRANT: N01-CO-12400

ACRONYM: CO

MEDLINETA: Cancer Gene Ther

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