Gene therapy for adenosine deaminase deficiency

Robertson Parkman; Kenneth Weinberg; Gay Crooks; Jan Nolta; Neena Kapoor; Donald Kohn

doi:10.1146/annurev.med.51.1.33

Gene therapy for adenosine deaminase deficiency

Robertson Parkman, Kenneth Weinberg, Gay Crooks, Jan Nolta, Neena Kapoor, Donald Kohn

Research output: Contribution to journal › Article › peer-review

27 Scopus citations

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	https://doi.org/10.1146/annurev.med.51.1.33
State	Published - 2000
Externally published	Yes

Keywords

Gene expression
Gene therapy
Hematopoietic stem cell
Primary immunodeficiency
Retroviral vector

ASJC Scopus subject areas

Cell Biology
Medicine(all)

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10.1146/annurev.med.51.1.33

Cite this

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title = "Gene therapy for adenosine deaminase deficiency",

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.",

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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

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Gene therapy for adenosine deaminase deficiency

Abstract

Keywords

ASJC Scopus subject areas

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