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 language | English (US) |
|---|---|
| Pages (from-to) | 775-780 |
| Number of pages | 6 |
| Journal | Nature Medicine |
| Volume | 4 |
| Issue number | 7 |
| DOIs | |
| State | Published - Jul 1998 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - Tlymphocytes with a normal ADA gene accumulate after transplantation of transduced autologous umbilical cord blood CD34+ cells in ADA-deficient SCID neonates
AU - Kohn, Donald B.
AU - Hershfield, Michael S.
AU - Carbonaro, Denise
AU - Shigeoka, Ann
AU - Brooks, Judith
AU - Smogorzewska, E. Monika
AU - Barsky, Lora W.
AU - Chan, Raymond
AU - Burotto, Felix
AU - Annett, Geralyn
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
PY - 1998/7
Y1 - 1998/7
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=0031593688&partnerID=8YFLogxK
U2 - 10.1038/nm0798-775
DO - 10.1038/nm0798-775
M3 - Article
VL - 4
SP - 775
EP - 780
JO - Nature Medicine
JF - Nature Medicine
SN - 1078-8956
IS - 7
ER -