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Clinical gene therapy in hematology: Past and future

Richter, Johan LU and Karlsson, Stefan LU (2001) In International Journal of Hematology 73(2). p.162-169
Abstract
Gene transfer into hematopoietic cells using viral vectors has focused mostly on lymphocytes and hematopoietic stem cells (HSCs). HSCs have been considered particularly important as target cells because of their pluripotency and ability to reconstitute hematopoiesis after myeloablation and transplantation. HSCs are believed to have the ability to live a long time, perhaps a lifetime, in the recipient following bone marrow transplantation. Genetic correction of HSCs can therefore potentially last a lifetime and permanently cure hematologic disorders in which genetic deficiencies cause the pathology. Oncoretroviral vectors have been the main vectors used for HSCs because of their ability to integrate into the chromosomes of their target... (More)
Gene transfer into hematopoietic cells using viral vectors has focused mostly on lymphocytes and hematopoietic stem cells (HSCs). HSCs have been considered particularly important as target cells because of their pluripotency and ability to reconstitute hematopoiesis after myeloablation and transplantation. HSCs are believed to have the ability to live a long time, perhaps a lifetime, in the recipient following bone marrow transplantation. Genetic correction of HSCs can therefore potentially last a lifetime and permanently cure hematologic disorders in which genetic deficiencies cause the pathology. Oncoretroviral vectors have been the main vectors used for HSCs because of their ability to integrate into the chromosomes of their target cells. Gene-transfer efficiency of murine HSCs is high using oncoretroviral vectors. In contrast, gene-transfer efficiency using the same viral vectors to transduce human HSCs or HSCs from large animals has been much lower. Although these difficulties may have several causes. the main reason for the low efficiency of human HSC transduction with oncoretroviral vectors is probably because of the nondividing nature of HSCs. Murine HSCs can be easily stimulated to divide in culture, whereas it is more problematic to stimulate human HSCs to divide rapidly in vitro. Because oncoretroviral vectors require dividing target cells for successful nuclear import of the preintegration complex and subsequent integration of the provirus, only the dividing fraction of the target cells can be transduced. This review focuses on gene transfer into human hematopoietic cells, particularly human HSCs. We review the clinical studies that have been reported, including the recent successful gene therapy for X-linked severe combined immunodeficiency. We discuss how the gene-transfer efficiency of human HSCs can be improved using oncoretroviral and lentiviral vectors. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Gene therapy, Lentiviral vectors, Retroviral vectors, Hematopoietic stem cells, Genetic diseases
in
International Journal of Hematology
volume
73
issue
2
pages
162 - 169
publisher
Carden Jennings Publishing Co., Ltd.
external identifiers
  • wos:000169400800005
  • scopus:0035261138
ISSN
0925-5710
language
English
LU publication?
yes
id
c3a327bc-869a-4d90-948f-e1ba0a9cce1d (old id 1119104)
date added to LUP
2008-07-11 13:50:46
date last changed
2018-05-29 11:30:00
@article{c3a327bc-869a-4d90-948f-e1ba0a9cce1d,
  abstract     = {Gene transfer into hematopoietic cells using viral vectors has focused mostly on lymphocytes and hematopoietic stem cells (HSCs). HSCs have been considered particularly important as target cells because of their pluripotency and ability to reconstitute hematopoiesis after myeloablation and transplantation. HSCs are believed to have the ability to live a long time, perhaps a lifetime, in the recipient following bone marrow transplantation. Genetic correction of HSCs can therefore potentially last a lifetime and permanently cure hematologic disorders in which genetic deficiencies cause the pathology. Oncoretroviral vectors have been the main vectors used for HSCs because of their ability to integrate into the chromosomes of their target cells. Gene-transfer efficiency of murine HSCs is high using oncoretroviral vectors. In contrast, gene-transfer efficiency using the same viral vectors to transduce human HSCs or HSCs from large animals has been much lower. Although these difficulties may have several causes. the main reason for the low efficiency of human HSC transduction with oncoretroviral vectors is probably because of the nondividing nature of HSCs. Murine HSCs can be easily stimulated to divide in culture, whereas it is more problematic to stimulate human HSCs to divide rapidly in vitro. Because oncoretroviral vectors require dividing target cells for successful nuclear import of the preintegration complex and subsequent integration of the provirus, only the dividing fraction of the target cells can be transduced. This review focuses on gene transfer into human hematopoietic cells, particularly human HSCs. We review the clinical studies that have been reported, including the recent successful gene therapy for X-linked severe combined immunodeficiency. We discuss how the gene-transfer efficiency of human HSCs can be improved using oncoretroviral and lentiviral vectors.},
  author       = {Richter, Johan and Karlsson, Stefan},
  issn         = {0925-5710},
  keyword      = {Gene therapy,Lentiviral vectors,Retroviral vectors,Hematopoietic stem cells,Genetic diseases},
  language     = {eng},
  number       = {2},
  pages        = {162--169},
  publisher    = {Carden Jennings Publishing Co., Ltd.},
  series       = {International Journal of Hematology},
  title        = {Clinical gene therapy in hematology: Past and future},
  volume       = {73},
  year         = {2001},
}