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.

  • Nonviral Transfer Technology
  • Published:

Widespread gene transfection into the central nervous system of primates

Abstract

We attempted in vivo gene transfection into the central nervous system (CNS) of non-human primates using the hemagglutinating virus of Japan (HVJ)-AVE liposome, a newly constructed anionic type liposome with a lipid composition similar to that of HIV envelopes and coated by the fusogenic envelope proteins of inactivated HVJ. HVJ-AVE liposomes containing the lacZ gene were applied intrathecally through the cisterna magna of Japanese macaques. Widespread transgene expression was observed mainly in the neurons. The lacZ gene was highly expressed in the medial temporal lobe, brainstem, Purkinje cells of cerebellar vermis and upper cervical cord (29.0 to 59.4% of neurons). Intrastriatal injection of an HVJ-AVE liposome–lacZ complex made a focal transfection around the injection sites up to 15 mm. We conclude that the infusion of HVJ-AVE liposomes into the cerebrospinal fluid (CSF) space is applicable for widespread gene delivery into the CNS of large animals.

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

Figure 1
Figure 3
Figure 2
Figure 4

Similar content being viewed by others

References

  1. Leiden JM . Gene therapy – promise, pitfalls, and prognosis New Engl J Med 1995 13: 871–873

    Article  Google Scholar 

  2. Wang C, Chao C, Maddedu P . Central delivery of human tissue kallikrein gene reduces blood pressure in hypertensive rats Biochem Biophys Res Commun 1998 244: 449–454

    Article  CAS  PubMed  Google Scholar 

  3. Mandel RJ, Spratt SK, Snyder RO . Midbrain injection of recombinant adeno-associated virus encoding rat glial cell line-derived neurotrophic factor protects nigral neurons in a progressive 6-hydroxydopamine-induced degeneration model of Parkinson's disease in rat Proc Natl Acad Sci USA 1997 94: 14083–14088

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Linnik MD, Zahos P, Geschwind MD . Expression of bcl-2 from a defective herpes simplex virus-1 vector limits neuronal death in focal cerebral ischemia Stroke 1995 26: 1670–1675

    Article  CAS  PubMed  Google Scholar 

  5. Lawrence MS, Ho DY, Sun GH . Overexpression of bcl-2 with herpes simplex virus vectors protects CNS neurons against neurological insults in vitro and in vivo J Neurosci 1996 15: 486–496

    Article  Google Scholar 

  6. Lawrence MS, McLaughlin JR, Sun G-H . Herpes simplex viral vectors expressing bcl-2 are neuroprotective when delivered after a stroke J Cereb Blood Flow Metab 1997 7: 740–744

    Article  Google Scholar 

  7. Blömer U, Naldini L, Kafri T . Highly efficient and sustained gene transfer in adult neurons with a lentivirus vector J Virol 1997 71: 6641–6649

    PubMed  PubMed Central  Google Scholar 

  8. Naldini L, Blömer U, Gage FH . Efficient transfer, integration, and sustained long-term expression of the transgene in adult rat brains injected with a lentiviral vector Proc Natl Acad Sci USA 1996 93: 11382–11388

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Yamada Y, Moriguchi A, Morishita R . Efficient oligonucleotide delivery using the HVJ-liposome method in the central nervous system Am J Physiol 1996 271: R1212–R1220

    Article  CAS  PubMed  Google Scholar 

  10. Kaneda Y et al. The improved efficient method for introducing macromolecules into cells using HVJ (Sendai virus) Exp Cell Res 1987 173: 56–69

    Article  CAS  PubMed  Google Scholar 

  11. Hirano T et al. Persistent gene expression in rat liver in vivo by repetitive transfections using HVJ-liposome Gene Therapy 1998 5: 459–464

    Article  CAS  PubMed  Google Scholar 

  12. Crystal RG . Transfer of genes to humans: early lessons and obstacles to success Science 1995 270: 404–410

    Article  CAS  PubMed  Google Scholar 

  13. Saeki Y et al. Developement and characterization of cationic liposomes conjugated with HVJ (Sendai virus): reciprocal effect of cationic lipid for in vitro and in vivo gene transfer Hum Gene Ther 1997 8: 2133–2141

    Article  CAS  PubMed  Google Scholar 

  14. Hagihara Y, Saitoh Y, Kaneda Y . Brain protection by the transfection of bcl-2 gene into the entire central nervous system (CNS) Rest Neurol Neurosci 1998 13: 221–235

    Google Scholar 

  15. Mabuchi E et al. Gene delivery by HVJ-liposome in the experimental gene therapy of murine glioma Gene Therapy 1997 4: 768–772

    Article  CAS  PubMed  Google Scholar 

  16. Baskar JF et al. The enhancer domain of the human cytomegalovirus major immediate–early promoter determines cell type specific expression in transgenic mice J Virol 1996 70: 3207–3214

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We greatly appreciate the technical support of Ichiro Fujita, Hiroyuki Yoneshima, Hisashi Tanigawa and Keisuke Kawasaki, Laboratory of Cognitive Neuroscience, Department of Biophysical engineering, Osaka University Graduate School of Engineering Science.

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hagihara, Y., Saitoh, Y., Kaneda, Y. et al. Widespread gene transfection into the central nervous system of primates. Gene Ther 7, 759–763 (2000). https://doi.org/10.1038/sj.gt.3301169

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.gt.3301169

Keywords

This article is cited by

Search

Quick links