Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Research Article
  • Published:

In vitro and in vivo gene delivery mediated by a synthetic polycationic amino polymer

Nature Biotechnology volume 15, pages 462–466 (1997)Cite this article

Abstract

A synthetic polyamino polymer with a glucose backbone was used for gene transfer in vitro and in vivo. Gene transfer in vitro to various human carcinoma cell lines was achieved with an efficiency superior to a commercially available cationic liposome preparation. The polymer was resistant to inhibition by serum, which allowed for efficient gene transfer in vivo. Direct intracranial tumor injection using this reagent resulted in reporter gene expression levels comparable to those achieved by a recombinant adenoviral vector. Thus, this compound represents a new class of agent that may have broad utility for gene transfer and gene therapy applications.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Lemarchand, P., Jones, M., Yamada, I. and Crystal, R.G. . 1993. In vivo gene transfer in normal uninjured blood vessels using replication-deficient recombinant adenoviral vectors. Circulation Res. 72: 1132–1138.

    Article  CAS  Google Scholar 

  2. Gao, X. and Huang, L. 1995. Cationic liposome-mediated gene delivery.Gene Therapy. 2: 10–722.

    Google Scholar 

  3. Feigner, P.L., Tsai, Y.J., Sukhu, L., Wheeler, C.J., Manthorpe, M., Marshall, J. et al. 1995. Improved cationic lipid formulations for in vivo gene therapy. [Review] Ann. N.Y. Acad. Sci. 772: 128–139.

    Google Scholar 

  4. Mizuguchi, H., Nakagawa, T., Nakanishi, M., Imazu, S., Nakagawa, S., Mayumi, T. 1996. Efficient gene transfer into mammalian cells using fuso-genic liposome. Bio. Biophys. Res. Comm. 218: 402–407.

    Article  CAS  Google Scholar 

  5. Sawa, Y., Suzuki, K., Bai, H.Z., Shirakura, R., Morishita, R., et al.1995. Efficiency of in vivo gene transfection into transplanted rat heart by coronary infusion of HVJ liposome. Circulation 92 (9 Suppl): 11479–ll482.

    Article  Google Scholar 

  6. Solodin, I., Brown, C.S., Bruno, M.S., Chow, C.Y., Jang, E.H., Debs, R.J. et al. 1995. A novel series of amphiphilic imidazolinium compounds for in vitro and in vivo gene delivery. Biochemistry 34: 13537–13544.

    Article  CAS  Google Scholar 

  7. Ooboshi, H., Welsh, M.J., Rios, C.D., Davidson, B.L. and Heistad, D.D. . 1995. Adenovirus-mediated gene transfer in vivo to cerebral blood vessels and perivascular tissue. Circulation Res. 77: 7–13.

    Article  CAS  Google Scholar 

  8. Boussif, O., Lezoualc'h, F., Zanta, M.A., Mergny, M.D., Scherman, D., Demeneix, B. et al. 1995. A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo polyethylenimine. Proc. Natl. Acad. Sci. USA 92: 7297–7301.

    Article  CAS  Google Scholar 

  9. Cook, D.R., Maxwell, I.H., Glode, L.M., Maxwell, F., Stevens, J.O., Purner, M.B. et al. 1994. Gene therapy for B-cell lymphoma in a SCID mouse model using an immunoglobulin-regulated diphtheria toxin gene delivered by a novel adenovirus-polylysine conjugate. Cancer Biotherapy 9: 131–141.

    Article  CAS  Google Scholar 

  10. Nabel, E.G., Gordon, D., Yang, Z.Y., Xu L, San, H., Plautz, G.E., et al. 1992. Gene transfer in vivo with DNA-liposome complexes lack of autoimmunity and gonadal localization. Hum. Gene Ther. 3: 649–656.

    Article  CAS  Google Scholar 

  11. Hoeben, R.C., Fallaux, F.J., Van Tilburg, N.H., Cramer, S.J., Van Ormondt, H., Briet, E. et al. 1993. Toward gene therapy for hemophilia A longterm persistence of factor Vlll-secreting fibroblasts after transplantation into immunodeficient mice.Hum. Gene Ther. 4: 179–186.

    Article  CAS  Google Scholar 

  12. Hanania, E.G., Kavanagh, J., Hortobagyi, G., Giles, R.E., Champlim, R., Deisseroth, A.B. . 1995. Recent advances in the application of gene therapy to human disease. [Review] Amer. J. Med. 99: 537–552.

    Article  CAS  Google Scholar 

  13. Thierry, A.R., Lunardi Iskandar Y, Bryant, J.L, Rabinovich, R, Gallo, R.C., and Mahan, L.C . 1995. Systemic gene delivery biodistribution and long-term expression of a transgene in mice. Proc.Natl. Acad. Sci. USA 92: 9742–9746.

    Article  CAS  Google Scholar 

  14. Schofield, J.P. and Caskey, C.T. . 1995. Non-viral approaches to gene therapy. [Review] Br. Med. Bull. 51: 56–71.

    Article  CAS  Google Scholar 

  15. Blasese, M., Blankenstein, T., Brenner, M., Cohen-Haguenauer, O., Gasnsbacher, B., Russel, S. et al. Vectors in cancer therapy how will they deliver? Cancer Gene Ther. 2;4: 291–297.

  16. Cao L, Zheng, Z.C., Zhao, Y.C., Jiang, Z.H., Liu, Z.G., Chen, S.D., et al. 1995. Gene therapy of Parkinson disease model rat by direct injection of plasmid DNA-lipofectin complex. Hum. Gene Ther. 6: 1497–1501.

    Article  CAS  Google Scholar 

  17. Yagi, K., Hayashi Y, Ishida, N., Ohbayashi, M., Ohishi, N., Mizuno, M., et al. 1994. Interferon-beta endogenously produced by intratumoral injection of cationic liposome-encapsulated gene: cytocidal effect on glioma transplanted into nude mouse brain. Biochem. Mol. Biol. Int. 32: 167–171.

    CAS  PubMed  Google Scholar 

  18. Roessler B.J. and Davidson, B.L. 1994. Direct plasmid mediated transfection of adult murine brain cells in vivo using cationic liposomes. Neurosci. Let. 167: 5–10.

    Article  CAS  Google Scholar 

  19. Lutz, J., Augustin, A.J., Jager, L.J., Bachmann, D. and Brandl, M. 1995. Acute toxicity and depression of phagocytosis in vivo by liposomes:influence of lysophosphatidylcholine. Life Sci. 56: 99–106.

    Article  CAS  Google Scholar 

  20. Sambrook, J., Fritsch, E.F. and Maniatis, T. 1989. Molecular cloning.2nd ed. Chapter 6, 6.2-6.13. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY.

    Google Scholar 

  21. Cubitt, A.B., Heim, R., Adams, S.R., Boyd, A.E., Gross, L.A. and Tsien, R.Y. 1995. Understanding, improving and using green fluorescent proteins. [Review] Trends Biochem. Sci. 20: 448–455.

    Article  CAS  Google Scholar 

  22. Teramoto, S., Johnson, L.G., Huang, W., Leigh, M.W. and Boucher, R.C. . 1995. Effect of adenoviral vector infection on cell proliferation in cultured primary human airway epithelial cells. Hum. Gene Ther. 6: 1045–1053.

    Article  CAS  Google Scholar 

  23. Vincent, M.C., Trapnell, B.C., Baughman, R.P., Wert, S.E., Whitsett, J.A. and Iwamoto, H.S. . 1995. Adenovirus-mediated gene transfer to the respiratory tract of fetal sheep in utero. Hum. Gene Ther. 6: 1019–1028.

    Article  CAS  Google Scholar 

  24. Bass, C., Cabrera, G., Elgavish, A., Robert, B., Siegal, G.R., Anderson, S.C. et al. 1995. Recombinant adenovirus-mediated gene transfer to genitourinary epithelium in vitro and in vivo.v Cancer Gene Ther. 2: 97–104.

    CAS  PubMed  Google Scholar 

  25. Lozier, J.N., Thompson, A.R., Hu, P.C., Read, M., Brinkhous, K.M. et al. 1994. Efficient transfection of primary cells in a canine hemophilia B model using adenovirus-polylysine-DNA complexes. Hum. Gene Ther. 5: 313–322.

    Article  CAS  Google Scholar 

  26. Muldoon, E.G., Nilaver, G., Kroll, R.A., Pagel M.A, Breakenfield, X.O., Chiocca, E.A., et al 1995. Comparison of intracerebral inoculation and osmotic blood-brain barrier disruption for delivery of adenovirus, herpesvirus, and iron oxide particles to normal rat brain. Amer. J. Pathol. 147: 1840–1851.

    CAS  Google Scholar 

  27. Enomaa, N., Danos, O., Peltonen, L. and Jalanko, A. 1995. Correction of deficient enzyme activity in a lysosomal storage disease, aspartylglu-cosaminuria, by enzyme replacement and retroviral gene transfer. Hum. Gene Ther. 6: 723–731.

    Article  CAS  Google Scholar 

  28. Szilvassy, S.J. and Gory, S. 1994. Efficient retroviral gene transfer to purified long-term repopulating hematopoietic stem cells. Blood 84: 74–83.

    CAS  PubMed  Google Scholar 

  29. Byrnes, A.R., Rusby, J.E., Wood, M.J. and Charlton, H.M. . 1995. Adenovirus gene transfer causes inflammation in the brain. Neuroscience 66: 1015–1024.

    Article  CAS  Google Scholar 

  30. Graham, F. and Prevec, L. 1991. Manipulation of adenovirus vectors, pp. 109–129 in Methods in molecular biology Vol 7, Gene Transfer and expression techniques. Murray, E.J. and Walker, J.M. (eds.). Humana Press, Clifton, NJ.

    Google Scholar 

Download references

Author information

Author notes

  1. David T. Curiel: Corresponding author: (e-mail: david.curiel@ccc.uab.edu).

Authors and Affiliations

  1. Gene Therapy Program, University of Alabama at Birmingham, Birmingham, AL, 35294

    Corey K. Goldman, Natalie Smith & Guadalupe Bilbao

  2. Division of Neurosurgery, University of Alabama at Birmingham, Birmingham, AL, 35294

    Liliana Soroceanu & G. Yancey Gillespie

  3. Avanti Polar Lipids, Alabaster, AL, 35007

    Walter Shaw & Steve Burgess

Authors
  1. Corey K. Goldman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Liliana Soroceanu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Natalie Smith
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. G. Yancey Gillespie
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Walter Shaw
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Steve Burgess
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Guadalupe Bilbao
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. David T. Curiel
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Goldman, C., Soroceanu, L., Smith, N. et al. In vitro and in vivo gene delivery mediated by a synthetic polycationic amino polymer. Nat Biotechnol 15, 462–466 (1997). https://doi.org/10.1038/nbt0597-462

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nbt0597-462

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing