Tlymphocytes with a normal ADA gene accumulate after transplantation of transduced autologous umbilical cord blood CD34+ cells in ADA-deficient SCID neonates

Donald B. Kohn, Michael S. Hershfield, Denise Carbonaro, Ann Shigeoka, Judith Brooks, E. Monika Smogorzewska, Lora W. Barsky, Raymond Chan, Felix Burotto, Geralyn Annett, Jan Nolta, Gay Crooks, Neena Kapoor, Melissa Elder, Diane Wara, Thomas Bowen, Edward Madsen, Floyd F. Snyder, John Bastian, Linda Muul & 3 others R. Michael Blaese, Kenneth Weinberg, Robertson Parkman

Research output: Contribution to journalArticle

260 Citations (Scopus)

Abstract

Adenosine deaminase-deficient severe combined immunodeficiency was the first disease investigated for gene therapy because of a postulated production or survival advantage for gene-corrected T lymphocytes, which may overcome inefficient gene transfer. Four years after three newborns with this disease were given infusions of transduced autologous umbilical cord blood CD34+ cells, the frequency of gene-containing T lymphocytes has risen to 1- 10%, whereas the frequencies of other hematopoietic and lymphoid cells containing the gene remain at 0.01-0.1%. Cessation of polyethylene glycol- conjugated adenosine deaminase enzyme replacement in one subject led to a decline in immune function, despite the persistence of gene-containing T lymphocytes. Thus, despite the long-term engraftment of transduced stem cells and selective accumulation of gene-containing T lymphocytes, improved gene transfer and expression will be needed to attain a therapeutic effect.

Original languageEnglish (US)
Pages (from-to)775-780
Number of pages6
JournalNature Medicine
Volume4
Issue number7
DOIs
StatePublished - Jul 1998
Externally publishedYes

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Autologous Transplantation
Fetal Blood
T-cells
Blood Cells
Blood
Genes
Gene transfer
T-Lymphocytes
Adenosine Deaminase
Gene therapy
Therapeutic Uses
Stem cells
Gene Frequency
Gene expression
Genetic Therapy
Stem Cells
Severe combined immunodeficiency due to adenosine deaminase deficiency
Lymphocytes
Gene Expression
Enzymes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Tlymphocytes with a normal ADA gene accumulate after transplantation of transduced autologous umbilical cord blood CD34+ cells in ADA-deficient SCID neonates. / Kohn, Donald B.; Hershfield, Michael S.; Carbonaro, Denise; Shigeoka, Ann; Brooks, Judith; Smogorzewska, E. Monika; Barsky, Lora W.; Chan, Raymond; Burotto, Felix; Annett, Geralyn; Nolta, Jan; Crooks, Gay; Kapoor, Neena; Elder, Melissa; Wara, Diane; Bowen, Thomas; Madsen, Edward; Snyder, Floyd F.; Bastian, John; Muul, Linda; Blaese, R. Michael; Weinberg, Kenneth; Parkman, Robertson.

In: Nature Medicine, Vol. 4, No. 7, 07.1998, p. 775-780.

Research output: Contribution to journalArticle

Kohn, DB, Hershfield, MS, Carbonaro, D, Shigeoka, A, Brooks, J, Smogorzewska, EM, Barsky, LW, Chan, R, Burotto, F, Annett, G, Nolta, J, Crooks, G, Kapoor, N, Elder, M, Wara, D, Bowen, T, Madsen, E, Snyder, FF, Bastian, J, Muul, L, Blaese, RM, Weinberg, K & Parkman, R 1998, 'Tlymphocytes with a normal ADA gene accumulate after transplantation of transduced autologous umbilical cord blood CD34+ cells in ADA-deficient SCID neonates', Nature Medicine, vol. 4, no. 7, pp. 775-780. https://doi.org/10.1038/nm0798-775
Kohn, Donald B. ; Hershfield, Michael S. ; Carbonaro, Denise ; Shigeoka, Ann ; Brooks, Judith ; Smogorzewska, E. Monika ; Barsky, Lora W. ; Chan, Raymond ; Burotto, Felix ; Annett, Geralyn ; Nolta, Jan ; Crooks, Gay ; Kapoor, Neena ; Elder, Melissa ; Wara, Diane ; Bowen, Thomas ; Madsen, Edward ; Snyder, Floyd F. ; Bastian, John ; Muul, Linda ; Blaese, R. Michael ; Weinberg, Kenneth ; Parkman, Robertson. / Tlymphocytes with a normal ADA gene accumulate after transplantation of transduced autologous umbilical cord blood CD34+ cells in ADA-deficient SCID neonates. In: Nature Medicine. 1998 ; Vol. 4, No. 7. pp. 775-780.
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AU - Brooks, Judith

AU - Smogorzewska, E. Monika

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AU - Nolta, Jan

AU - Crooks, Gay

AU - Kapoor, Neena

AU - Elder, Melissa

AU - Wara, Diane

AU - Bowen, Thomas

AU - Madsen, Edward

AU - Snyder, Floyd F.

AU - Bastian, John

AU - Muul, Linda

AU - Blaese, R. Michael

AU - Weinberg, Kenneth

AU - Parkman, Robertson

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