Differences in gene expression between sonoporation in tumor and in muscle

Tsai, Keh‐Chyuan; Liao, Zhe Kang; Yang, Shu; Lin, Wen Chang; Shieh, Ming Jium; Hwang, Lih Hwa; Chen, Wen-Shiang

doi:10.1002/jgm.1376

Cited by 28 publications

(25 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1). Our results are in agreement with another recent report that demonstrated that muscle was more amenable to ultrasound-and nanobubble-mediated gene transfer than were subcutaneous or orthotropic tumors (32). In addition, we demonstrated that gene transfer mediated by ultrasound and nanobubbles can also be performed on mice with arthritis or muscle degeneration, suggesting that these pathologies do not impair the transduction potential of the methodology.…”

Section: Discussionsupporting

confidence: 93%

Delivery of Na/I Symporter Gene into Skeletal Muscle Using Nanobubbles and Ultrasound: Visualization of Gene Expression by PET

Watanabe¹,

Horie²,

Funaki³

et al. 2010

J Nucl Med

View full text Add to dashboard Cite

The development of nonviral gene delivery systems is essential in gene therapy, and the use of a minimally invasive imaging methodology can provide important clinical endpoints. In the current study, we present a new methodology for gene therapy-a delivery system using nanobubbles and ultrasound as a nonviral gene delivery method. We assessed whether the gene transfer allowed by this methodology was detectable by PET and bioluminescence imaging. Methods: Two kinds of reported vectors (luciferase and human Na/I symporter [hNIS]) were transfected or cotransfected into the skeletal muscles of normal mice (BALB/c) using the ultrasound-nanobubbles method. The kinetics of luciferase gene expression were analyzed in vivo using bioluminescence imaging. At the peak of gene transfer, PET of hNIS expression was performed using our recently developed PET scanner, after 124 I injection. The imaging data were confirmed using reverse-transcriptase polymerase chain reaction amplification, biodistribution, and a blocking study. The imaging potential of the 2 methodologies was evaluated in 2 mouse models of human pathology (McH/lpr-RA1 mice showing vascular disease and C57BL/10-mdx Jic mice showing muscular dystrophy). Results: Peak luciferase gene activity was observed in the skeletal muscle 4 d after transfection. On day 2 after hNIS and luciferase cotransfection, the expression of these genes was confirmed by reverse-transcriptase polymerase chain reaction on a muscle biopsy. PET of the hNIS gene, biodistribution, the blocking study, and autoradiography were performed on day 4 after transfection, and it was indicated that hNIS expression was restricted to the site of plasmid administration (skeletal muscle). Similar localized PET and 124 I accumulation were successfully obtained in the diseasemodel mice. Conclusion: The hNIS gene was delivered into the skeletal muscle of healthy and disease-model mice by the ultrasound-nanobubbles method, and gene expression was successfully visualized with PET. The combination of ultrasound-nanobubble gene transfer and PET may be applied to gene therapy clinical protocols.

show abstract

Section: Discussionsupporting

confidence: 93%

Delivery of Na/I Symporter Gene into Skeletal Muscle Using Nanobubbles and Ultrasound: Visualization of Gene Expression by PET

Watanabe¹,

Horie²,

Funaki³

et al. 2010

J Nucl Med

View full text Add to dashboard Cite

show abstract

“…Optison and SonoVue MB have been shown to mediate transfection of pLuc in muscle and tumor with similar efficiencies following sonoporation (Tsai et al, 2009). Our results suggest that although the exact equivalency in dosage between Ad and sonoporated plasmids is difficult to achieve, at the doses used (Pislaru et al, 2003;Passineau et al, 2010), our imaging data suggested that the sonoporation method can be about four times (in vivo) to *10 times (ex vivo) more efficient than Ad.…”

Section: Discussionmentioning

confidence: 45%

“…For example, sonoporation has been used to deliver reporter genes encoding B-galactosidase (Hauff et al, 2005), enhanced green fluorescent protein (Tsai et al, 2009), and luciferase (Aoi et al, 2008;Li et al, 2009). These sonoporation approaches are also being applied to cancer therapy.…”

Section: Discussionmentioning

confidence: 98%

Sonoporation Delivery of Interleukin-27 Gene Therapy Efficiently Reduces Prostate Tumor Cell Growth In Vivo

et al. 2011

View full text Add to dashboard Cite

We have examined the potential of a novel cytokine, interleukin-27 (IL-27), for gene therapy of prostate cancer. IL-27 is the most recently characterized member of the family of heterodimeric IL-12-related cytokines and has shown promise in halting tumor growth and mediating tumor regression in several cancer models. In the present study, we examined the efficacy of a new mode of gene delivery to prostate tumors: low-frequency ultrasound irradiation or "sonoporation." We also examined the potential of IL-27 gene delivery by sonoporation to treat and reduce the growth of prostate cancer in vivo. We used three models of immune-competent prostate adenocarcinoma and characterized the tumor-growth reduction, gene-profile expression, and effector cellular profiles. Our results suggest that IL-27 can be effective in reducing tumor growth and can help enhance accumulation of effector cells in prostate tumors in vivo. These results are promising, because they are potentially relevant to developing novel therapies that can be translated by using the novel and effective sonoporation gene-therapy delivery strategy.

show abstract

“…However, the half-lives of the anti-angiogenic proteins in circulation are usually short (for example, in vivo decay of endostatin is bi-exponential, resulting in a half-life (t 1/2 ) of 42.3 min and a b t 1/2 of 12.9 h), 37 which may result in disappointing therapeutic effects when used in clinical treatment. 33 On the other hand, DNA delivered into the muscle can be retained in the tissue for up to 1 week, 26 thus enabling the production of anti-angiogenic proteins over a longer period of time. The expression can be further sustained with repeated US treatments.…”

Section: Discussionmentioning

confidence: 99%

“…In this context, our previous study demonstrates that US-mediated gene delivery is more effective in muscle tissue than in tumors. 26 The goal of the current study is to test the therapeutic effect of US-mediated intramuscular expression of anti-angiogenic genes on distant orthotopic tumors. Our results show that repeated US administration to deliver endostatin (ED) or calreticulin (CRT) genes to muscle led to a significant antitumor effect on distant orthotopic tumors in the liver, brain or lungs.…”

Section: Introductionmentioning

confidence: 99%

Sonoporation-mediated anti-angiogenic gene transfer into muscle effectively regresses distant orthotopic tumors

et al. 2011

View full text Add to dashboard Cite

Ultrasound (US) is an effective tool for local delivery of genes into target tumors or organs. In combination with microbubbles, US can temporarily change the permeability of cell membranes by cavitation and facilitate entry of plasmid DNA into cells. Here, we demonstrate that repeated US-mediated delivery of anti-angiogenic genes, endostatin or calreticulin, into muscle significantly inhibits the growth of orthotopic tumors in the liver, brain or lung. US-mediated anti-angiogenic gene therapy also seems to function as an adjuvant therapy that significantly enhances the antitumor effects of the chemotherapeutic drug doxorubicin and adenovirus-mediated cytokine gene therapy. Significantly higher levels of tumor apoptosis or tumor-infiltrating lymphocytes were observed after combined therapy consisting of either anti-angiogenic therapy and chemotherapy, or anti-angiogenic therapy and immunotherapy. Taken together, our experiments demonstrate that intramuscular delivery of anti-angiogenic genes by US exposure can effectively treat distant orthotopic tumors, and thus has great therapeutic potential in terms of clinical treatment.

show abstract

Differences in gene expression between sonoporation in tumor and in muscle

Abstract: The present study indicates that muscle tissue is a good target site for producing large amounts of gene products for the purpose of gene therapy.

Cited by 28 publications

References 30 publications

Delivery of Na/I Symporter Gene into Skeletal Muscle Using Nanobubbles and Ultrasound: Visualization of Gene Expression by PET

Delivery of Na/I Symporter Gene into Skeletal Muscle Using Nanobubbles and Ultrasound: Visualization of Gene Expression by PET

Sonoporation Delivery of Interleukin-27 Gene Therapy Efficiently Reduces Prostate Tumor Cell Growth In Vivo

Sonoporation-mediated anti-angiogenic gene transfer into muscle effectively regresses distant orthotopic tumors

Contact Info

Product

Resources

About