Abstract
The clinical gene therapy trials for adenosine deaminase (ADA) deficiency have defined both the potential benefits and the present limitations of gene therapy with hematopoietic stem cells (HSC). Current clinical results indicate that (a) both umbilical cord blood and neonatal bone marrow HSC can be transduced with murine retroviral-based vectors, (b) the transduced HSC can engraft in nonmyeloablated patients, (c) the frequency of HSC transduction/engraftment is low (1/10,000), (6) an in vivo selective advantage can exist for transduced T lymphoid progeny, and (e) the transduced ADA gene is not expressed in nondividing T lymphocytes. Improving the clinical results of gene therapy for ADA deficiency and other genetic diseases involving HSC will require (a) developing new vectors that express the transduced gene in nondividing cells and (b) increasing the frequency of stable HSC transduction.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 33-47 |
| Number of pages | 15 |
| Journal | Annual Review of Medicine |
| Volume | 51 |
| DOIs | |
| State | Published - 2000 |
| Externally published | Yes |
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Keywords
- Gene expression
- Gene therapy
- Hematopoietic stem cell
- Primary immunodeficiency
- Retroviral vector
ASJC Scopus subject areas
- Cell Biology
- Medicine(all)
Cite this
Gene therapy for adenosine deaminase deficiency. / Parkman, Robertson; Weinberg, Kenneth; Crooks, Gay; Nolta, Jan; Kapoor, Neena; Kohn, Donald.
In: Annual Review of Medicine, Vol. 51, 2000, p. 33-47.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Gene therapy for adenosine deaminase deficiency
AU - Parkman, Robertson
AU - Weinberg, Kenneth
AU - Crooks, Gay
AU - Nolta, Jan
AU - Kapoor, Neena
AU - Kohn, Donald
PY - 2000
Y1 - 2000
N2 - The clinical gene therapy trials for adenosine deaminase (ADA) deficiency have defined both the potential benefits and the present limitations of gene therapy with hematopoietic stem cells (HSC). Current clinical results indicate that (a) both umbilical cord blood and neonatal bone marrow HSC can be transduced with murine retroviral-based vectors, (b) the transduced HSC can engraft in nonmyeloablated patients, (c) the frequency of HSC transduction/engraftment is low (1/10,000), (6) an in vivo selective advantage can exist for transduced T lymphoid progeny, and (e) the transduced ADA gene is not expressed in nondividing T lymphocytes. Improving the clinical results of gene therapy for ADA deficiency and other genetic diseases involving HSC will require (a) developing new vectors that express the transduced gene in nondividing cells and (b) increasing the frequency of stable HSC transduction.
AB - The clinical gene therapy trials for adenosine deaminase (ADA) deficiency have defined both the potential benefits and the present limitations of gene therapy with hematopoietic stem cells (HSC). Current clinical results indicate that (a) both umbilical cord blood and neonatal bone marrow HSC can be transduced with murine retroviral-based vectors, (b) the transduced HSC can engraft in nonmyeloablated patients, (c) the frequency of HSC transduction/engraftment is low (1/10,000), (6) an in vivo selective advantage can exist for transduced T lymphoid progeny, and (e) the transduced ADA gene is not expressed in nondividing T lymphocytes. Improving the clinical results of gene therapy for ADA deficiency and other genetic diseases involving HSC will require (a) developing new vectors that express the transduced gene in nondividing cells and (b) increasing the frequency of stable HSC transduction.
KW - Gene expression
KW - Gene therapy
KW - Hematopoietic stem cell
KW - Primary immunodeficiency
KW - Retroviral vector
UR - http://www.scopus.com/inward/record.url?scp=0034093243&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034093243&partnerID=8YFLogxK
U2 - 10.1146/annurev.med.51.1.33
DO - 10.1146/annurev.med.51.1.33
M3 - Article
VL - 51
SP - 33
EP - 47
JO - Annual Review of Medicine
JF - Annual Review of Medicine
SN - 0066-4219
ER -