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 MuulR. Michael Blaese, Kenneth Weinberg, Robertson Parkman

Research output: Contribution to journalArticlepeer-review

262 Scopus citations


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
Issue number7
StatePublished - Jul 1998
Externally publishedYes

ASJC Scopus subject areas

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


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