Side effects of retroviral gene transfer into hematopoietic stem cells
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Side effects of retroviral gene transfer into hematopoietic stem cells. / Baum, Christopher; Düllmann, Jochen; Li, Zhixiong; Fehse, Boris; Meyer, Johann; Williams, David A; von Kalle, Christof.
In: BLOOD, Vol. 101, No. 6, 15.03.2003, p. 2099-114.Research output: SCORING: Contribution to journal › SCORING: Review article › Research
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TY - JOUR
T1 - Side effects of retroviral gene transfer into hematopoietic stem cells
AU - Baum, Christopher
AU - Düllmann, Jochen
AU - Li, Zhixiong
AU - Fehse, Boris
AU - Meyer, Johann
AU - Williams, David A
AU - von Kalle, Christof
PY - 2003/3/15
Y1 - 2003/3/15
N2 - Recent conceptual and technical improvements have resulted in clinically meaningful levels of gene transfer into repopulating hematopoietic stem cells. At the same time, evidence is accumulating that gene therapy may induce several kinds of unexpected side effects, based on preclinical and clinical data. To assess the therapeutic potential of genetic interventions in hematopoietic cells, it will be important to derive a classification of side effects, to obtain insights into their underlying mechanisms, and to use rigorous statistical approaches in comparing data. We here review side effects related to target cell manipulation; vector production; transgene insertion and expression; selection procedures for transgenic cells; and immune surveillance. We also address some inherent differences between hematopoiesis in the most commonly used animal model, the laboratory mouse, and in humans. It is our intention to emphasize the need for a critical and hypothesis-driven analysis of "transgene toxicology," in order to improve safety, efficiency, and prognosis for the yet small but expanding group of patients that could benefit from gene therapy.
AB - Recent conceptual and technical improvements have resulted in clinically meaningful levels of gene transfer into repopulating hematopoietic stem cells. At the same time, evidence is accumulating that gene therapy may induce several kinds of unexpected side effects, based on preclinical and clinical data. To assess the therapeutic potential of genetic interventions in hematopoietic cells, it will be important to derive a classification of side effects, to obtain insights into their underlying mechanisms, and to use rigorous statistical approaches in comparing data. We here review side effects related to target cell manipulation; vector production; transgene insertion and expression; selection procedures for transgenic cells; and immune surveillance. We also address some inherent differences between hematopoiesis in the most commonly used animal model, the laboratory mouse, and in humans. It is our intention to emphasize the need for a critical and hypothesis-driven analysis of "transgene toxicology," in order to improve safety, efficiency, and prognosis for the yet small but expanding group of patients that could benefit from gene therapy.
KW - Animals
KW - Gene Expression
KW - Gene Transfer Techniques/adverse effects
KW - Genetic Therapy/adverse effects
KW - Genetic Vectors
KW - Hematopoiesis
KW - Hematopoietic Stem Cell Transplantation
KW - Hematopoietic Stem Cells
KW - Humans
KW - Immunity
KW - Retroviridae/genetics
KW - Risk Factors
KW - Transfection
U2 - 10.1182/blood-2002-07-2314
DO - 10.1182/blood-2002-07-2314
M3 - SCORING: Review article
C2 - 12511419
VL - 101
SP - 2099
EP - 2114
JO - BLOOD
JF - BLOOD
SN - 0006-4971
IS - 6
ER -
