Intravenous Delivery of Naked Plasmid DNA for in Vivo Cytokine Expression

doi:10.1006/bbrc.2001.6100

Biochemical and Biophysical Research Communications

Volume 289, Issue 5, 21 December 2001, Pages 1088-1092

https://doi.org/10.1006/bbrc.2001.6100 Get rights and content

Abstract

We previously demonstrated that electroporation-mediated cytokine gene delivery into muscle is an effective approach for long-term systemic delivery of cytokines. Here we show that hydrodynamics-based gene delivery into mice by intravenous administration of naked plasmid DNA is a more efficient procedure for expressing cytokines in vivo. A large volume of Ringer's solution containing an interleukin-10 (IL-10) expression plasmid pCAGGS-IL10 was rapidly injected into the tail vein of mice. Serum IL-10 levels increased in a dose-dependent manner with a saturation level (50.8 ± 12.1 μg/ml) 10,000-fold higher than we obtained by the electroporation-mediated method. High levels of serum IL-10 were sustained for at least 2 weeks following a single injection. These results demonstrate that hydrodynamics-based gene delivery could induce sustained high-level expression of cytokines, which would be useful for further studies of cytokine function in vivo and the development of novel immunotherapeutic strategies for systemic cytokine gene therapy.

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Citation Excerpt :
The mice were housed at the Frederick National Laboratory for Cancer Research (Frederick, MD) in a temperature-controlled, light-cycled facility and were cared for under the guidelines of the Frederick National Laboratory Animal Care and Use Committee. Hydrodynamic DNA injection was performed in BALB/c mice as described previously (30, 34–36), using endotoxin-free preparation of DNA (Qiagen, Hilden, Germany). Briefly, cytokine DNA was suspended in 1.6 ml of sterile 0.9% NaCl and was injected into mice through their tail vein in a 7-s push, using a 27.5-gauge needle.
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^☆: Abbreviations used: IL-10, interleukin-10; CAG promoter, modified chicken β-actin promoter with CMV-IE enhancer; ELISA, enzyme-linked immunosorbent assay; PBS, phosphate-buffered saline; ALT, alanine aminotransferase; X-gal, 5-bromo-4-chloro-3-indolyl-β- $d$ -galactopyranoside.

¹: To whom correspondence should be addressed. Fax: +81-6-6879-3829. E-mail: [email protected].

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Biochemical and Biophysical Research Communications

Abstract

References (27)

Cytokine imbalance in the pathogenesis of rheumatoid arthritis: The role of interleukin-1 receptor antagonist

Semin. Arthritis Rheum.

Use of retroviral vectors for gene transfer and expression

Methods Enzymol.

Gene therapy: Adenovirus vectors

Curr. Opin. Gen. Dev.

Adeno-associated virus vectors

Curr. Opin. Biotechnol.

Direct gene transfer into donor hearts at the time of harvest

J. Thorac. Cardiovasc. Surg.

In vivo gene delivery by electroporation

Adv. Drug Deliv. Rev.

IL-12 indirectly enhances proliferation of 5-FU-treated human hematopoietic peripheral blood CD34⁺ cells

Am. J. Hematol.

Thrombopoietin and megakaryocyte differentiation

Schweiz. Med. Wochenschr.

Interleukin-18 regulates both Th1 and Th2 responses

Annu. Rev. Immunol.

Cytokines in temporomandibular joint arthritis

Oral. Dis.

Th2 cytokine role in autoimmune haemolytic anaemia (AIHA) pathogenesis

Panminerva Med.

Cytokine and anti-cytokine therapy in chronic inflammatory bowel diseases

Dtsch. Med. Wochenschr.

Consideration of cytokines as therapeutics agents or targets

Curr. Pharm. Des.

Cited by (67)

Could artificial intelligence revolutionize the development of nanovectors for gene therapy and mRNA vaccines?

Multimeric RNAs for efficient RNA-based therapeutics and vaccines

Genetically modified mesenchymal stromal cells in cancer therapy

Regulation of autophagy by systemic admission of microRNA-141 to target HMGB1 in l-arginine-induced acute pancreatitis in vivo

The p40 subunit of interleukin (IL)-12 promotes stabilization and export of the p35 subunit: Implications for improved IL-12 cytokine production

Gene Delivery Using Physical Methods

Regular ArticleIntravenous Delivery of Naked Plasmid DNA for in Vivo Cytokine Expression☆

Abstract

Semin. Arthritis Rheum.

Methods Enzymol.

Curr. Opin. Gen. Dev.

Curr. Opin. Biotechnol.

J. Thorac. Cardiovasc. Surg.

Adv. Drug Deliv. Rev.

IL-12 indirectly enhances proliferation of 5-FU-treated human hematopoietic peripheral blood CD34+ cells

Am. J. Hematol.

Thrombopoietin and megakaryocyte differentiation

Schweiz. Med. Wochenschr.

Interleukin-18 regulates both Th1 and Th2 responses

Annu. Rev. Immunol.

Cytokines in temporomandibular joint arthritis

Oral. Dis.

Th2 cytokine role in autoimmune haemolytic anaemia (AIHA) pathogenesis

Panminerva Med.

Cytokine and anti-cytokine therapy in chronic inflammatory bowel diseases

Dtsch. Med. Wochenschr.

Consideration of cytokines as therapeutics agents or targets

Curr. Pharm. Des.

Regular Article
Intravenous Delivery of Naked Plasmid DNA for in Vivo Cytokine Expression☆

IL-12 indirectly enhances proliferation of 5-FU-treated human hematopoietic peripheral blood CD34⁺ cells