This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Onodera, M.
Right arrow Articles by Blaese, R. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Onodera, M.
Right arrow Articles by Blaese, R. M.

 Previous Article  |  Next Article 

J Virol, March 1998, p. 1769-1774, Vol. 72, No. 3
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Development of Improved Adenosine Deaminase Retroviral Vectors

Masafumi Onodera,1 David M. Nelson,1 Akihiro Yachie,2 G. Jayashree Jagadeesh,1 Bruce A. Bunnell,1 Richard A. Morgan,1 and R. Michael Blaese1,*

Clinical Gene Therapy Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892-1852,1 and Department of Pediatrics, Kanazawa University School of Medicine, 13-1, Takaramachi, Kanazawa 920, Japan2

Received 13 August 1997/Accepted 20 November 1997

A series of adenosine deaminase (ADA) retroviral vectors were designed and constructed with the goal of improved performance over the PA317/LASN vector currently used in clinical trials. First, the bacterial selectable-marker neomycin phosphotransferase (neo) gene was removed to create a "simplified" vector. Second, the Moloney murine leukemia virus long terminal repeat (LTR) promoter used for ADA expression was replaced with either the myeloproliferative sarcoma virus (MPSV) or SL3-3 LTR. Supernatant from each ADA vector was used to transduce ADA-deficient (ADA-) B- and T-cell lines as well as primary peripheral blood mononuclear cells (PBMC) from an ADA- severe combined immunodeficiency patient. Total ADA enzyme activity and ADA activity per integrant in the transduced cells demonstrated that the MPSV LTR splicing vector design provided the highest level of ADA expression per cell. This ADA(MPSV) vector was then tested in packaging cell lines containing either the gibbon ape leukemia virus envelope (PG13 cells), the murine amphotropic envelope (FLYA13 cells), or the feline endogenous virus RD114 envelope (FLYRD18 cells). The results indicate that FLYRD18/ADA(MPSV), a simplified ADA retroviral vector with the MPSV LTR, provides a 17-fold-higher level of ADA expression in human lymphohematopoietic cells than the PA317/LASN vector currently in use.

* Corresponding author. Mailing address: Clinical Gene Therapy Branch, NHGRI, NIH, Building 10, Room 10C103, 10 Center Dr., MSC 1852, Bethesda, MD 20892-1852. Phone: (301) 402-2544. Fax: (301) 496-7184. E-mail: mblaese{at}nhgri.nih.gov.




This article has been cited by other articles:

  • Engel, B. C., Podsakoff, G. M., Ireland, J. L., Smogorzewska, E. M., Carbonaro, D. A., Wilson, K., Shah, A., Kapoor, N., Sweeney, M., Borchert, M., Crooks, G. M., Weinberg, K. I., Parkman, R., Rosenblatt, H. M., Wu, S.-Q., Hershfield, M. S., Candotti, F., Kohn, D. B. (2007). Prolonged pancytopenia in a gene therapy patient with ADA-deficient SCID and trisomy 8 mosaicism: a case report. Blood 109: 503-506 [Abstract] [Full Text]  
  • Zhao, Y., Zheng, Z., Robbins, P. F., Khong, H. T., Rosenberg, S. A., Morgan, R. A. (2005). Primary Human Lymphocytes Transduced with NY-ESO-1 Antigen-Specific TCR Genes Recognize and Kill Diverse Human Tumor Cell Lines. J. Immunol. 174: 4415-4423 [Abstract] [Full Text]  
  • Morgan, R. A., Dudley, M. E., Yu, Y. Y. L., Zheng, Z., Robbins, P. F., Theoret, M. R., Wunderlich, J. R., Hughes, M. S., Restifo, N. P., Rosenberg, S. A. (2003). High Efficiency TCR Gene Transfer into Primary Human Lymphocytes Affords Avid Recognition of Melanoma Tumor Antigen Glycoprotein 100 and Does Not Alter the Recognition of Autologous Melanoma Antigens. J. Immunol. 171: 3287-3295 [Abstract] [Full Text]  
  • Goerner, M., Horn, P. A., Peterson, L., Kurre, P., Storb, R., Rasko, J. E. J., Kiem, H.-P. (2001). Sustained multilineage gene persistence and expression in dogs transplanted with CD34+ marrow cells transduced by RD114-pseudotype oncoretrovirus vectors. Blood 98: 2065-2070 [Abstract] [Full Text]  
  • Williams, D. A., Nienhuis, A. W., Hawley, R. G., Smith, F. O. (2000). Gene Therapy 2000. ASH Education Book 2000: 376-393 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»