Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1995 Jan 31;92(3):699–703. doi: 10.1073/pnas.92.3.699

Intracellular immunization of human fetal cord blood stem/progenitor cells with a ribozyme against human immunodeficiency virus type 1.

M Yu 1, M C Leavitt 1, M Maruyama 1, O Yamada 1, D Young 1, A D Ho 1, F Wong-Staal 1
PMCID: PMC42687  PMID: 7531339

Abstract

Successful treatment of human immunodeficiency virus infection may ultimately require targeting of hematopoietic stem cells. Here we used retroviral vectors carrying the ribozyme gene to transduce CD34+ cells from human fetal cord blood. Transduction and ribozyme expression had no apparent adverse effect on cell differentiation and/or proliferation. The macrophage-like cells, differentiated from the stem/progenitor cells in vitro, expressed the ribozyme gene and resisted infection by a macrophage tropic human immunodeficiency virus type 1. These results suggest the feasibility of stem cell gene therapy for human immunodeficiency virus-infected patients.

Full text

PDF
699

Images in this article

700Fig. 1
on p.700
701Fig. 2
on p.701
701Fig. 3
on p.701

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Baltimore D. Gene therapy. Intracellular immunization. Nature. 1988 Sep 29;335(6189):395–396. doi: 10.1038/335395a0. [DOI] [PubMed] [Google Scholar]
  2. Broxmeyer H. E., Douglas G. W., Hangoc G., Cooper S., Bard J., English D., Arny M., Thomas L., Boyse E. A. Human umbilical cord blood as a potential source of transplantable hematopoietic stem/progenitor cells. Proc Natl Acad Sci U S A. 1989 May;86(10):3828–3832. doi: 10.1073/pnas.86.10.3828. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Broxmeyer H. E., Hangoc G., Cooper S., Ribeiro R. C., Graves V., Yoder M., Wagner J., Vadhan-Raj S., Benninger L., Rubinstein P. Growth characteristics and expansion of human umbilical cord blood and estimation of its potential for transplantation in adults. Proc Natl Acad Sci U S A. 1992 May 1;89(9):4109–4113. doi: 10.1073/pnas.89.9.4109. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cardoso A. A., Li M. L., Batard P., Hatzfeld A., Brown E. L., Levesque J. P., Sookdeo H., Panterne B., Sansilvestri P., Clark S. C. Release from quiescence of CD34+ CD38- human umbilical cord blood cells reveals their potentiality to engraft adults. Proc Natl Acad Sci U S A. 1993 Sep 15;90(18):8707–8711. doi: 10.1073/pnas.90.18.8707. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cotten M., Birnstiel M. L. Ribozyme mediated destruction of RNA in vivo. EMBO J. 1989 Dec 1;8(12):3861–3866. doi: 10.1002/j.1460-2075.1989.tb08564.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Fauci A. S. Multifactorial nature of human immunodeficiency virus disease: implications for therapy. Science. 1993 Nov 12;262(5136):1011–1018. doi: 10.1126/science.8235617. [DOI] [PubMed] [Google Scholar]
  7. Folks T. M., Kessler S. W., Orenstein J. M., Justement J. S., Jaffe E. S., Fauci A. S. Infection and replication of HIV-1 in purified progenitor cells of normal human bone marrow. Science. 1988 Nov 11;242(4880):919–922. doi: 10.1126/science.2460922. [DOI] [PubMed] [Google Scholar]
  8. Hows J. M., Bradley B. A., Marsh J. C., Luft T., Coutinho L., Testa N. G., Dexter T. M. Growth of human umbilical-cord blood in longterm haemopoietic cultures. Lancet. 1992 Jul 11;340(8811):73–76. doi: 10.1016/0140-6736(92)90396-k. [DOI] [PubMed] [Google Scholar]
  9. Huang S., Terstappen L. W. Lymphoid and myeloid differentiation of single human CD34+, HLA-DR+, CD38- hematopoietic stem cells. Blood. 1994 Mar 15;83(6):1515–1526. [PubMed] [Google Scholar]
  10. Jenks S. Infants' gene therapy gains easy RAC approval. J Natl Cancer Inst. 1993 Jul 21;85(14):1108–1109. doi: 10.1093/jnci/85.14.1108. [DOI] [PubMed] [Google Scholar]
  11. Jennings P. A., Molloy P. L. Inhibition of SV40 replicon function by engineered antisense RNA transcribed by RNA polymerase III. EMBO J. 1987 Oct;6(10):3043–3047. doi: 10.1002/j.1460-2075.1987.tb02610.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Leavitt M. C., Yu M., Yamada O., Kraus G., Looney D., Poeschla E., Wong-Staal F. Transfer of an anti-HIV-1 ribozyme gene into primary human lymphocytes. Hum Gene Ther. 1994 Sep;5(9):1115–1120. doi: 10.1089/hum.1994.5.9-1115. [DOI] [PubMed] [Google Scholar]
  13. Lu L., Xiao M., Clapp D. W., Li Z. H., Broxmeyer H. E. High efficiency retroviral mediated gene transduction into single isolated immature and replatable CD34(3+) hematopoietic stem/progenitor cells from human umbilical cord blood. J Exp Med. 1993 Dec 1;178(6):2089–2096. doi: 10.1084/jem.178.6.2089. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Lu L., Xiao M., Shen R. N., Grigsby S., Broxmeyer H. E. Enrichment, characterization, and responsiveness of single primitive CD34 human umbilical cord blood hematopoietic progenitors with high proliferative and replating potential. Blood. 1993 Jan 1;81(1):41–48. [PubMed] [Google Scholar]
  15. Lu M., Maruyama M., Zhang N., Levine F., Friedmann T., Ho A. D. High efficiency retroviral-mediated gene transduction into CD34+ cells purified from peripheral blood of breast cancer patients primed with chemotherapy and granulocyte-macrophage colony-stimulating factor. Hum Gene Ther. 1994 Feb;5(2):203–208. doi: 10.1089/hum.1994.5.2-203. [DOI] [PubMed] [Google Scholar]
  16. Miller D. G., Adam M. A., Miller A. D. Gene transfer by retrovirus vectors occurs only in cells that are actively replicating at the time of infection. Mol Cell Biol. 1990 Aug;10(8):4239–4242. doi: 10.1128/mcb.10.8.4239. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Moritz T., Keller D. C., Williams D. A. Human cord blood cells as targets for gene transfer: potential use in genetic therapies of severe combined immunodeficiency disease. J Exp Med. 1993 Aug 1;178(2):529–536. doi: 10.1084/jem.178.2.529. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Ojwang J. O., Hampel A., Looney D. J., Wong-Staal F., Rappaport J. Inhibition of human immunodeficiency virus type 1 expression by a hairpin ribozyme. Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10802–10806. doi: 10.1073/pnas.89.22.10802. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Ryder R. W., Nsa W., Hassig S. E., Behets F., Rayfield M., Ekungola B., Nelson A. M., Mulenda U., Francis H., Mwandagalirwa K. Perinatal transmission of the human immunodeficiency virus type 1 to infants of seropositive women in Zaire. N Engl J Med. 1989 Jun 22;320(25):1637–1642. doi: 10.1056/NEJM198906223202501. [DOI] [PubMed] [Google Scholar]
  20. Scott G. B., Hutto C., Makuch R. W., Mastrucci M. T., O'Connor T., Mitchell C. D., Trapido E. J., Parks W. P. Survival in children with perinatally acquired human immunodeficiency virus type 1 infection. N Engl J Med. 1989 Dec 28;321(26):1791–1796. doi: 10.1056/NEJM198912283212604. [DOI] [PubMed] [Google Scholar]
  21. Sullenger B. A., Lee T. C., Smith C. A., Ungers G. E., Gilboa E. Expression of chimeric tRNA-driven antisense transcripts renders NIH 3T3 cells highly resistant to Moloney murine leukemia virus replication. Mol Cell Biol. 1990 Dec;10(12):6512–6523. doi: 10.1128/mcb.10.12.6512. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Tjønnfjord G. E., Veiby O. P., Steen R., Egeland T. T lymphocyte differentiation in vitro from adult human prethymic CD34+ bone marrow cells. J Exp Med. 1993 Jun 1;177(6):1531–1539. doi: 10.1084/jem.177.6.1531. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Yamada O., Yu M., Yee J. K., Kraus G., Looney D., Wong-Staal F. Intracellular immunization of human T cells with a hairpin ribozyme against human immunodeficiency virus type 1. Gene Ther. 1994 Jan;1(1):38–45. [PubMed] [Google Scholar]
  24. Yu M., Ojwang J., Yamada O., Hampel A., Rapapport J., Looney D., Wong-Staal F. A hairpin ribozyme inhibits expression of diverse strains of human immunodeficiency virus type 1. Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6340–6344. doi: 10.1073/pnas.90.13.6340. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Yu M., Poeschla E., Wong-Staal F. Progress towards gene therapy for HIV infection. Gene Ther. 1994 Jan;1(1):13–26. [PubMed] [Google Scholar]
  26. Zauli G., Re M. C., Visani G., Furlini G., Mazza P., Vignoli M., La Placa M. Evidence for a human immunodeficiency virus type 1-mediated suppression of uninfected hematopoietic (CD34+) cells in AIDS patients. J Infect Dis. 1992 Oct;166(4):710–716. doi: 10.1093/infdis/166.4.710. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES