Skip to main content
PMC 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
. 1986 Sep;83(17):6563–6567. doi: 10.1073/pnas.83.17.6563

Correction of adenosine deaminase deficiency in cultured human T and B cells by retrovirus-mediated gene transfer.

P W Kantoff, D B Kohn, H Mitsuya, D Armentano, M Sieberg, J A Zwiebel, M A Eglitis, J R McLachlin, D A Wiginton, J J Hutton, et al.
PMCID: PMC386544  PMID: 3489233

Abstract

A retroviral vector called SAX, containing the cloned human cDNA for adenosine deaminase (ADA), has been constructed and used to introduce the ADA gene into cultured T- and B-lymphocyte lines derived from patients with ADA deficiency. DNA analysis showed that the SAX vector was inserted intact into the T and B cells at approximately one copy per cell. The treated cells produced the characteristic isozymes of human ADA at a level similar to normal T and B lymphocytes. It is known that ADA-deficient lymphocytes are unusually sensitive to high levels of 2'-deoxyadenosine, and this is the mechanism thought to underlie the selective lymphocytotoxicity associated with ADA deficiency in vivo. Expression of the introduced ADA gene was sufficient to reverse the hypersensitivity of these genetically deficient lymphocytes to 2'-deoxyadenosine toxicity. These results support the suggestion that retroviral vector gene-delivery systems show promise for application to human gene therapy.

Full text

PDF
6566

Images in this article

6565Image
on p.6565
6565Image
on p.6565

Selected References

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

  1. Adrian G. S., Wiginton D. A., Hutton J. J. Characterization of normal and mutant adenosine deaminase messenger RNAs by translation and hybridization to a cDNA probe. Hum Genet. 1984;68(2):169–172. doi: 10.1007/BF00279309. [DOI] [PubMed] [Google Scholar]
  2. Adrian G. S., Wiginton D. A., Hutton J. J. Structure of adenosine deaminase mRNAs from normal and adenosine deaminase-deficient human cell lines. Mol Cell Biol. 1984 Sep;4(9):1712–1717. doi: 10.1128/mcb.4.9.1712. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Agarwal R. P., Spector T., Parks R. E., Jr Tight-binding inhibitors--IV. Inhibition of adenosine deaminases by various inhibitors. Biochem Pharmacol. 1977 Mar 1;26(5):359–367. doi: 10.1016/0006-2952(77)90192-7. [DOI] [PubMed] [Google Scholar]
  4. Anderson W. F. Prospects for human gene therapy. Science. 1984 Oct 26;226(4673):401–409. doi: 10.1126/science.6093246. [DOI] [PubMed] [Google Scholar]
  5. Cohen A., Hirschhorn R., Horowitz S. D., Rubinstein A., Polmar S. H., Hong R., Martin D. W., Jr Deoxyadenosine triphosphate as a potentially toxic metabolite in adenosine deaminase deficiency. Proc Natl Acad Sci U S A. 1978 Jan;75(1):472–476. doi: 10.1073/pnas.75.1.472. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Coleman M. S., Donofrio J., Hutton J. J., Hahn L., Daoud A., Lampkin B., Dyminski J. Identification and quantitation of adenine deoxynucleotides in erythrocytes of a patient with adenosine deaminase deficiency and severe combined immunodeficiency. J Biol Chem. 1978 Mar 10;253(5):1619–1626. [PubMed] [Google Scholar]
  7. Daddona P. E., Kelley W. N. Characteristics of an aminohydrolase distinct from adenosine deaminase in cultured human lymphoblasts. Biochim Biophys Acta. 1981 Apr 14;658(2):280–290. doi: 10.1016/0005-2744(81)90298-9. [DOI] [PubMed] [Google Scholar]
  8. Dick J. E., Magli M. C., Huszar D., Phillips R. A., Bernstein A. Introduction of a selectable gene into primitive stem cells capable of long-term reconstitution of the hemopoietic system of W/Wv mice. Cell. 1985 Aug;42(1):71–79. doi: 10.1016/s0092-8674(85)80102-1. [DOI] [PubMed] [Google Scholar]
  9. Dyminski J. W., Daoud A., Lampkin B. C., Limouze S., Donofrio J., Coleman M. S., Hutton J. J. Immunological and biochemical profiles in response to transfusion therapy in an adenosine deaminase-deficient patient with severe combined immunodeficiency disease. Clin Immunol Immunopathol. 1979 Nov;14(3):307–326. doi: 10.1016/0090-1229(79)90157-0. [DOI] [PubMed] [Google Scholar]
  10. Eglitis M. A., Kantoff P., Gilboa E., Anderson W. F. Gene expression in mice after high efficiency retroviral-mediated gene transfer. Science. 1985 Dec 20;230(4732):1395–1398. doi: 10.1126/science.2999985. [DOI] [PubMed] [Google Scholar]
  11. Fox I. H., Kelley W. N. The role of adenosine and 2'-deoxyadenosine in mammalian cells. Annu Rev Biochem. 1978;47:655–686. doi: 10.1146/annurev.bi.47.070178.003255. [DOI] [PubMed] [Google Scholar]
  12. Friedman R. L. Expression of human adenosine deaminase using a transmissable murine retrovirus vector system. Proc Natl Acad Sci U S A. 1985 Feb;82(3):703–707. doi: 10.1073/pnas.82.3.703. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Giblett E. R., Anderson J. E., Cohen F., Pollara B., Meuwissen H. J. Adenosine-deaminase deficiency in two patients with severely impaired cellular immunity. Lancet. 1972 Nov 18;2(7786):1067–1069. doi: 10.1016/s0140-6736(72)92345-8. [DOI] [PubMed] [Google Scholar]
  14. Gross-Bellard M., Oudet P., Chambon P. Isolation of high-molecular-weight DNA from mammalian cells. Eur J Biochem. 1973 Jul 2;36(1):32–38. doi: 10.1111/j.1432-1033.1973.tb02881.x. [DOI] [PubMed] [Google Scholar]
  15. Gruber H. E., Finley K. D., Hershberg R. M., Katzman S. S., Laikind P. K., Seegmiller J. E., Friedmann T., Yee J. K., Jolly D. J. Retroviral vector-mediated gene transfer into human hematopoietic progenitor cells. Science. 1985 Nov 29;230(4729):1057–1061. doi: 10.1126/science.3864246. [DOI] [PubMed] [Google Scholar]
  16. Hirschhorn R., Bajaj S., Borkowsky W., Kowalski A., Hong R., Rubinstein A., Papageorgiou P. Differential inhibition of adenosine deaminase deficient peripheral blood lymphocytes and lymphoid line cells by deoxyadenosine and adenosine. Cell Immunol. 1979 Feb;42(2):418–423. doi: 10.1016/0008-8749(79)90207-7. [DOI] [PubMed] [Google Scholar]
  17. Hirschhorn R., Vawter G. F., Kirkpatrick J. A., Jr, Rosen F. S. Adenosine deaminase deficiency: frequency and comparative pathology in autosomally recessive severe combined immunodeficiency. Clin Immunol Immunopathol. 1979 Sep;14(1):107–120. doi: 10.1016/0090-1229(79)90131-4. [DOI] [PubMed] [Google Scholar]
  18. Hutton J. J., Wiginton D. A., Coleman M. S., Fuller S. A., Limouze S., Lampkin B. C. Biochemical and functional abnormalities in lymphocytes from an adenosine deaminase-deficient patient during enzyme replacement therapy. J Clin Invest. 1981 Aug;68(2):413–421. doi: 10.1172/JCI110270. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Joyner A., Keller G., Phillips R. A., Bernstein A. Retrovirus transfer of a bacterial gene into mouse haematopoietic progenitor cells. Nature. 1983 Oct 6;305(5934):556–558. doi: 10.1038/305556a0. [DOI] [PubMed] [Google Scholar]
  20. Keller G., Paige C., Gilboa E., Wagner E. F. Expression of a foreign gene in myeloid and lymphoid cells derived from multipotent haematopoietic precursors. Nature. 1985 Nov 14;318(6042):149–154. doi: 10.1038/318149a0. [DOI] [PubMed] [Google Scholar]
  21. Lang R. A., Metcalf D., Gough N. M., Dunn A. R., Gonda T. J. Expression of a hemopoietic growth factor cDNA in a factor-dependent cell line results in autonomous growth and tumorigenicity. Cell. 1985 Dec;43(2 Pt 1):531–542. doi: 10.1016/0092-8674(85)90182-5. [DOI] [PubMed] [Google Scholar]
  22. Miller A. D., Eckner R. J., Jolly D. J., Friedmann T., Verma I. M. Expression of a retrovirus encoding human HPRT in mice. Science. 1984 Aug 10;225(4662):630–632. doi: 10.1126/science.6377498. [DOI] [PubMed] [Google Scholar]
  23. Miller A. D., Jolly D. J., Friedmann T., Verma I. M. A transmissible retrovirus expressing human hypoxanthine phosphoribosyltransferase (HPRT): gene transfer into cells obtained from humans deficient in HPRT. Proc Natl Acad Sci U S A. 1983 Aug;80(15):4709–4713. doi: 10.1073/pnas.80.15.4709. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Mitsuya H., Guo H. G., Megson M., Trainor C., Reitz M. S., Jr, Broder S. Transformation and cytopathogenic effect in an immune human T-cell clone infected by HTLV-I. Science. 1984 Mar 23;223(4642):1293–1296. doi: 10.1126/science.6322299. [DOI] [PubMed] [Google Scholar]
  25. Polmar S. H., Stern R. C., Schwartz A. L., Wetzler E. M., Chase P. A., Hirschhorn R. Enzyme replacement therapy for adenosine deaminase deficiency and severe combined immunodeficiency. N Engl J Med. 1976 Dec 9;295(24):1337–1343. doi: 10.1056/NEJM197612092952402. [DOI] [PubMed] [Google Scholar]
  26. Schrader W. P., Pollara B., Meuwissen H. J. Characterization of the residual adenosine deaminating activity in the spleen of a patient with combined immunodeficiency disease and adenosine deaminase deficiency. Proc Natl Acad Sci U S A. 1978 Jan;75(1):446–450. doi: 10.1073/pnas.75.1.446. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  28. Wigler M., Silverstein S., Lee L. S., Pellicer A., Cheng Y. c., Axel R. Transfer of purified herpes virus thymidine kinase gene to cultured mouse cells. Cell. 1977 May;11(1):223–232. doi: 10.1016/0092-8674(77)90333-6. [DOI] [PubMed] [Google Scholar]
  29. Williams D. A., Lemischka I. R., Nathan D. G., Mulligan R. C. Introduction of new genetic material into pluripotent haematopoietic stem cells of the mouse. Nature. 1984 Aug 9;310(5977):476–480. doi: 10.1038/310476a0. [DOI] [PubMed] [Google Scholar]
  30. van der Weyden M. B., Bailey L. A micromethod for determining adenosine deaminase and purine nucleoside phosphorylase activity in cells from human peripheral blood. Clin Chim Acta. 1978 Jan 2;82(1-2):179–184. doi: 10.1016/0009-8981(78)90041-4. [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