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Bioanalysis
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Future Drug Discovery
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International Journal of Pharmacokinetics
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Therapeutic Delivery
Preliminary Communication

A nonviral vector with transfection activity comparable with adenoviral transduction

    Jennifer Cheung

    Department of Biomedical Sciences, Arthur A. Dugoni School of Dentistry, University of the Pacific, 155 Fifth Street, San Francisco, CA 94103, USA

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    ,
    Takahiro Chino

    Department of Biomedical Sciences, Arthur A. Dugoni School of Dentistry, University of the Pacific, 155 Fifth Street, San Francisco, CA 94103, USA

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    ,
    Cynthia Co

    Dental Surgery Program, Arthur A. Dugoni School of Dentistry, University of the Pacific, 155 Fifth Street, San Francisco, CA 94103, USA

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    ,
    Krystyna Konopka

    Department of Biomedical Sciences, Arthur A. Dugoni School of Dentistry, University of the Pacific, 155 Fifth Street, San Francisco, CA 94103, USA

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    &
    Nejat Düzgünes

    *Author for correspondence:

    E-mail Address: nduzgunes@pacific.edu

    Department of Biomedical Sciences, Arthur A. Dugoni School of Dentistry, University of the Pacific, 155 Fifth Street, San Francisco, CA 94103, USA

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    Published Online:28 Oct 2016https://doi.org/10.4155/tde-2016-0054

    Abstract

    Aim: Viral vectors are used commonly in gene therapy trials, but their potential toxic effects are a serious concern. Identification of highly efficient nonviral vectors may alleviate these effects. Results & methodology: We compared the abilities of TransfeX, TransIT-LT1 and adenovirus to deliver the firefly luciferase and green fluorescent protein genes into HeLa cervical carcinoma, and HSC-3 and H357 oral squamous cell carcinoma cells. TransfeX mediated fourfold higher gene expression in HeLa cells than adenovirus, even at the highest multiplicity of infection. Flow cytometry indicated that a population of transfected cells expresses higher levels of green fluorescent protein than transduced cells. Conclusion: TransfeX may be useful for gene therapy applications, particularly where the use of adenovirus is contraindicated.

    Papers of special note have been highlighted as: • of interest

    References

    • 1 Thomas SM, Grandis JR. Current state of head and neck cancer gene therapy. Hum. Gene Ther. 20, 1565–1575 (2009).
      Medline CASGoogle Scholar
    • 2 Walther W, Schlag PM. Current status of gene therapy for cancer. Curr. Opin. Oncol. 25, 659–664 (2013).
      Medline CASGoogle Scholar
    • 3 Zallen DT. US gene therapy in crisis. Trends Genet. 16, 272–275 (2000).
      MedlineGoogle Scholar
    • 4 Raper SE, Chirmule N, Lee FS et al. Fatal systemic inflammatory response syndrome in a ornithine transcarbamylase deficient patient following adenoviral gene transfer. Mol. Genet. Metab. 80, 148–158 (2003).
      Medline CASGoogle Scholar
    • 5 Tousignant JD, Gates AL, Ingram LA et al. Comprehensive analysis of the acute toxicities induced by systemic administration of cationic lipid:plasmid DNA complexes in mice. Hum. Gene Ther. 11, 2493–2513 (2000).
      Medline CASGoogle Scholar
    • 6 Sakurai H, Sakurai F, Kawabata K et al. Comparison of gene expression efficiency and innate immune response induced by Ad vector and lipoplex. J. Control. Release. 117, 430–437 (2007). • Shows that adenovirus vectors mediate much higher levels of gene expression in vivo than lipoplexes.
      Medline CASGoogle Scholar
    • 7 Lonez C, Vandenbranden M, Elouahabi A, Ruysschaert JM. Cationic lipid/DNA complexes induce TNF-alpha secretion in splenic macrophages. Eur. J. Pharm. Biopharm. 69, 817–823 (2008).
      Medline CASGoogle Scholar
    • 8 Hama S, Akita H, Iida S, Mizuguchi H, Harashima H. Quantitative and mechanism-based investigation of post-nuclear delivery events between adenovirus and lipoplex. Nucleic Acids Res. 35, 1533–1543 (2007).
      Medline CASGoogle Scholar
    • 9 Tros de Ilarduya C, Sun Y, Düzgüneş N. Gene delivery by lipoplexes and polyplexes. Eur. J. Pharm. Sci. 40, 159–170 (2010). • A thorough but concise review of the field.
      Medline CASGoogle Scholar
    • 10 McGraw SL, Ferrante JM. Update on prevention and screening of cervical cancer. World J. Clin. Oncol. 5, 744–752 (2014).
      MedlineGoogle Scholar
    • 11 Rousseau A, Badoual C. Head and neck: squamous cell carcinoma: an overview. Atlas Genet. Cytogenet. Oncol. Haematol. 16, 145–155 (2012).
      Google Scholar
    • 12 Konopka K, Lee A, Moser-Kim N et al. Gene transfer to human oral cancer cells via non-viral vectors and HSV-tk/ganciclovir-mediated cytotoxicity: potential for suicide gene therapy. Gene Ther. Mol. Biol. 8, 307–318 (2004).
      Google Scholar
    • 13 Lavorini-Doyle C, Gebremedhin S, Konopka K, Düzgüneş N. Gene delivery to oral cancer cells by nonviral vectors: why some cells are resistant to transfection. J. Calif. Dent. Assoc. 37, 855–858 (2009).
      MedlineGoogle Scholar
    • 14 Konopka N, Fallah B, Monzon-Duller J, Overlid N, Lim A, Düzgüneş N. Serum-resistant gene transfer to oral cancer cells by Metafectene and GeneJammer: application to HSV-tk/ganciclovir-mediated cytotoxicity. Cell Mol. Biol. Lett. 10, 455–470 (2005).
      Medline CASGoogle Scholar
    • 15 Bergelson JM, Cunningham JA, Droguett G et al. Isolation of a common receptor for Coxsackie B viruses and adenoviruses 2 and 5. Science 275, 1320–1323 (1997).
      Medline CASGoogle Scholar
    • 16 Saito K, Sakaguchi M, Iioka H et al. Coxsackie and adenovirus receptor is a critical regulator for the survival and growth of oral squamous carcinoma cells. Oncogene 33, 1274–1286 (2014). • Reports the relative Coxsackie and adenovirus receptor mRNA expression in numerous cell lines.
      Medline CASGoogle Scholar
    • 17 Dilber MS, Abedi MR, Björkstrand B et al. Suicide gene therapy for plasma cell tumors. Blood 88, 2192–2200 (1996).
      Medline CASGoogle Scholar
    • 18 Düzgüneş N. Sitimagene ceradenovec, a gene therapeutic for the treatment of glioma. Curr. Opin. Mol. Ther. 10, 187–195 (2008).
      MedlineGoogle Scholar
    • 19 Gebremedhin S, Singh A, Koons S, Bernt W, Konopka K, Düzgüneş N. Gene delivery to carcinoma cells with novel non-viral vectors: nanoparticle tracking analysis and suicide gene therapy. Eur. J. Pharm. Sci. 60, 72–79 (2014). • Reports the first use of nanoparticle tracking analysis to determine the size of lipoplexes.
      Medline CASGoogle Scholar
    • 20 Neves SS, Faneca H, Bertin S et al. Transferrin-lipoplex-mediated suicide gene therapy of oral squamous cell carcinoma in an immunocompetent murine model and mechanisms involved in the antitumoral response. Cancer Gene Ther. 16, 91–101 (2009). • Demonstrates the inhibition of the growth of orthotopic oral cancer tumors by suicide gene therapy via transferrin lipoplexes.
      Medline CASGoogle Scholar
    • 21 Simões S, Slepushkin V, Gaspar R, Pedroso de Lima MC, Düzgüneş N. Gene delivery by negatively charged ternary complexes of DNA, cationic liposomes and transferrin or fusigenic peptides. Gene Ther. 5, 955–964 (1998).
      Medline CASGoogle Scholar
    • 22 Konopka K, Düzgüneş N, Rossi JJ, Lee NS. Receptor ligand-facilitated cationic liposome delivery of anti-HIV-1 Rev-binding aptamer and ribozyme DNAs. J. Drug Target. 5, 247–259 (1998).
      Medline CASGoogle Scholar
    • 23 Tros de Ilarduya C, Arangoa MA, Moreno-Aliaga MJ, Düzgüneş N. Enhanced gene delivery in vitro and in vivo by improved transferrin-lipoplexes. Biochim. Biophys. Acta 1561, 209–221 (2002).
      Medline CASGoogle Scholar
    • 24 Arangoa MA, Düzgüneş N, Tros de Ilarduya C. Increased receptor-mediated gene delivery to the liver by protamine-enhanced asialofetuin-lipoplexes. Gene Ther. 10, 5–14 (2003).
      Medline CASGoogle Scholar
    • 25 Tros de Ilarduya C, Buñuales M, Qian C, Düzgüneş N. Antitumoral activity of transferrin-lipoplexes carrying the IL-12 gene in the treatment of colon cancer. J. Drug Target. 14, 527–535 (2006).
      MedlineGoogle Scholar
    • 26 Buñuales M, Düzgüneş N, Zalba S, Garrido MJ, Tros de Ilarduya C. Efficient gene delivery by EGF-lipoplexes in vitro and in vivo. Nanomedicine (Lond.) 6, 89–98 (2011). • Demonstrates the use of a targeting ligand for gene delivery in vivo.
      Medline CASGoogle Scholar
    • 27 Tros de Ilarduya C, Düzgüneş N. Delivery of therapeutic nucleic acids via transferrin and transferrin receptors: lipoplexes and other carriers. Expert Opin. Drug Deliv. 10(11), 1–9 (2013).
      MedlineGoogle Scholar
    • 28 Düzgüneş N. Non-viral vectors for gene therapy. Cell Gene Ther. Insights 2(1), 1–3 (2016). • Emphasizes the inherent specificity of nonviral vector-mediated gene expression for rapidly dividing cells, and hence their potential for use in cancer gene therapy.
      Google Scholar