TY - JOUR
T1 - The continuing contribution of gene marking to cell and gene therapy
AU - Tey, Siok Keen
AU - Brenner, Malcolm K.
PY - 2007/4
Y1 - 2007/4
N2 - Gene-marking studies were the first gene-transfer protocols approved for human use. Their intent was not directly therapeutic but rather to track the behavior and fate of cells in vivo, and to use this information to improve treatment protocols. For more than fifteen years, gene-marking studies using retroviral vectors have provided invaluable information about the biology of human hematopoietic cells and T lymphocytes, and have helped guide cell therapies intended to treat malignant disease. Although the safety record of marking studies has been impeccable, the development of leukemia by immunodeficient children treated with retroviral vectors cast a pall over the entire field and essentially brought the era of pure gene-marking studies to an abrupt end. Paradoxically, the impetus these events gave to studying retroviral integration sites in host cell DNA emphasized the additional information that marker studies could provide about the behavior of cells at the clonal level. As confidence has slowly returned, marker studies have reappeared, usually as components of gene therapy protocols in which a marker gene or sequence is incorporated to allow the modified cells to be tracked or imaged in vivo. Hence, gene marking continues to have much to offer in terms of our understanding of the behavior, fate, and safety of gene-modified cells in vivo.
AB - Gene-marking studies were the first gene-transfer protocols approved for human use. Their intent was not directly therapeutic but rather to track the behavior and fate of cells in vivo, and to use this information to improve treatment protocols. For more than fifteen years, gene-marking studies using retroviral vectors have provided invaluable information about the biology of human hematopoietic cells and T lymphocytes, and have helped guide cell therapies intended to treat malignant disease. Although the safety record of marking studies has been impeccable, the development of leukemia by immunodeficient children treated with retroviral vectors cast a pall over the entire field and essentially brought the era of pure gene-marking studies to an abrupt end. Paradoxically, the impetus these events gave to studying retroviral integration sites in host cell DNA emphasized the additional information that marker studies could provide about the behavior of cells at the clonal level. As confidence has slowly returned, marker studies have reappeared, usually as components of gene therapy protocols in which a marker gene or sequence is incorporated to allow the modified cells to be tracked or imaged in vivo. Hence, gene marking continues to have much to offer in terms of our understanding of the behavior, fate, and safety of gene-modified cells in vivo.
UR - http://www.scopus.com/inward/record.url?scp=33947210724&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33947210724&partnerID=8YFLogxK
U2 - 10.1038/sj.mt.6300109
DO - 10.1038/sj.mt.6300109
M3 - Review article
C2 - 17299400
AN - SCOPUS:33947210724
VL - 15
SP - 666
EP - 676
JO - Molecular therapy : the journal of the American Society of Gene Therapy
JF - Molecular therapy : the journal of the American Society of Gene Therapy
SN - 1525-0016
IS - 4
ER -