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.

  • Millennium Review
  • Published:

Nonviral gene therapy: promises and challenges

Abstract

The last 10 years have seen substantial progress in the development and application of nonviral vectors in gene therapy. However, many problems remain to be resolved before nonviral gene therapy can become a standard clinical practice. This review highlights the major breakthroughs in this field. The problems and future research directions are also discussed.

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

Access options

Buy this article

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

Similar content being viewed by others

References

  1. Wolff JA et al. Direct gene transfer into mouse muscle in vivo Science 1990 247: 1465–1468

    Article  CAS  Google Scholar 

  2. Ulmer JB et al. Heterologous protection against influenza by injection of DNA encoding a viral protein Science 1993 259: 1745–1749

    Article  CAS  Google Scholar 

  3. Condon C et al. DNA-based immunization by in vivo transfection of dendritic cells Nature Med 1996 2: 1122–1128

    Article  CAS  Google Scholar 

  4. Liu F, Song Y, Liu D . Hydrodynamics-based transfection in animals by systemic administration of plasmid DNA Gene Therapy 1999 6: 1258–1266

    Article  CAS  Google Scholar 

  5. Yang NS et al. In vivo and in vitro gene transfer to mammalian somatic cells by particle bombardment Proc Natl Acad Sci USA 1990 87: 9568–9572

    Article  CAS  Google Scholar 

  6. Rols MP et al. In vivo electrically mediated protein and gene transfer in murine melanoma Nat Biotechnol 1998 16: 168–171

    Article  CAS  Google Scholar 

  7. Rizzuto G et al. Efficient and regulated erythropoietin production by naked DNA injection and muscle electroporation Proc Natl Acad Sci USA 1999 96: 6417–6422

    Article  CAS  Google Scholar 

  8. Anwer K et al. Systemic effect of human growth hormone after intramuscular injection of a single dose of a muscle-specific gene medicine Hum Gene Ther 1998 9: 659–670

    Article  CAS  Google Scholar 

  9. Felgner PL et al. Lipofection: a highly efficient, lipid-mediated DNA-transfection procedure Proc Natl Acad Sci USA 1987 84: 7413–7417

    Article  CAS  Google Scholar 

  10. Wheeler CJ et al. A novel cationic lipid greatly enhances plasmid DNA delivery and expression in mouse lung Proc Natl Acad Sci USA 1996 93: 11454–11459

    Article  CAS  Google Scholar 

  11. Lee ER et al. Detailed analysis of structures and formulations of cationic lipids for efficient gene transfer to the lung Hum Gene Ther 1996 7: 1701–1717

    Article  CAS  Google Scholar 

  12. Nabel GJ et al. Direct gene transfer with DNA–liposome complexes in melanoma: expression, biologic activity, and lack of toxicity in humans Proc Natl Acad Sci USA 1993 90: 11307–11311

    Article  CAS  Google Scholar 

  13. Caplen NJ et al. Liposome-mediated CFTR gene transfer to the nasal epithelium of patients with cystic fibrosis Nat Med 1995 1: 39–46

    Article  CAS  Google Scholar 

  14. Radler JO, Koltover I, Salditt T, Safinya CR . Structure of DNA–cationic liposome complexes: DNA intercalation in multilamellar membranes in distinct interhelical packing regimes Science 1997 275: 810–814

    Article  CAS  Google Scholar 

  15. Subramanian A, Ranganathan P, Diamond SL . Nuclear targeting peptide scaffolds for lipofection of nondividing mammalian cells Nat Biotechnol 1999 17: 873–877

    Article  CAS  Google Scholar 

  16. Li S et al. Dynamic changes in the characteristics of cationic lipidic vectors after exposure to mouse serum: implications for intravenous lipofection Gene Therapy 1999 6: 585–594

    Article  CAS  Google Scholar 

  17. Gao X, Huang L . Potentiation of cationic liposome-mediated gene delivery by polycations Biochemistry 1996 35: 1027–1036

    Article  CAS  Google Scholar 

  18. Liu Y et al. Factors influencing the efficiency of cationic liposome-mediated intravenous gene delivery Nat Biotechnol 1997 15: 167–173

    Article  CAS  Google Scholar 

  19. Boussif O et al. A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: polyethylenimine Proc Natl Acad Sci USA 1995 92: 7297–7301

    Article  CAS  Google Scholar 

  20. Roy K, Mao HQ, Huang SK, Leong KW . Oral gene delivery with chitosan–DNA nanoparticles generates immunologic protection in a murine model of peanut allergy Nat Med 1999 5: 387–391

    Article  CAS  Google Scholar 

  21. Cole-Strauss et al. Correction of the mutation responsible for sickle cell anemia by an RNA–DNA oligonucleotide Science 1996 273: 1386–1389

    Article  CAS  Google Scholar 

  22. Kren BT et al. Correction of the UDP-glucuronosyltransferase gene defect in the Gunn rat model of Crigler–Najjar syndrome type I with a chimeric oligonucleotide Proc Natl Acad Sci USA 1999 96: 10349–10354

    Article  CAS  Google Scholar 

  23. Yew NS et al. Contribution of plasmid DNA to inflammation in the lung after administration of cationic lipid:pDNA complexes Hum Gene Ther 1999 10: 223–234

    Article  CAS  Google Scholar 

  24. Li S et al. Effect of immune response on gene transfer to the lung via systemic administration of cationic lipidic vectors Am J Physiol 1999 276: L796–L804

    Article  CAS  Google Scholar 

  25. Krieg AM et al. CpG motifs in bacterial DNA trigger direct B-cell activation Nature 1995 374: 546–549

    Article  CAS  Google Scholar 

  26. Chu RS et al. CpG oligodeoxy-nucleotides act as adjuvants that switch on T helper 1 (Th1) immunity J Exp Med 1997 186: 1623–1631

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The original work in this laboratory was supported by NIH grants CA 59327, DK 44935, CA 71731 and a contract from Targeted Genetics Corporation.

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Li, S., Huang, L. Nonviral gene therapy: promises and challenges. Gene Ther 7, 31–34 (2000). https://doi.org/10.1038/sj.gt.3301110

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.gt.3301110

Keywords

This article is cited by

Search

Quick links