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Macrophages in gene therapy: cellular delivery vehicles and in vivo targets

Research output: Contribution to journalLiterature review

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Macrophages in gene therapy: cellular delivery vehicles and in vivo targets. / Burke, B; Sumner, S; Maitland, N; Lewis, C E.

In: Journal of leukocyte biology, Vol. 72, No. 3, 09.2002, p. 417-428.

Research output: Contribution to journalLiterature review

Harvard

Burke, B, Sumner, S, Maitland, N & Lewis, CE 2002, 'Macrophages in gene therapy: cellular delivery vehicles and in vivo targets', Journal of leukocyte biology, vol. 72, no. 3, pp. 417-428.

APA

Burke, B., Sumner, S., Maitland, N., & Lewis, C. E. (2002). Macrophages in gene therapy: cellular delivery vehicles and in vivo targets. Journal of leukocyte biology, 72(3), 417-428.

Vancouver

Burke B, Sumner S, Maitland N, Lewis CE. Macrophages in gene therapy: cellular delivery vehicles and in vivo targets. Journal of leukocyte biology. 2002 Sep;72(3):417-428.

Author

Burke, B ; Sumner, S ; Maitland, N ; Lewis, C E. / Macrophages in gene therapy: cellular delivery vehicles and in vivo targets. In: Journal of leukocyte biology. 2002 ; Vol. 72, No. 3. pp. 417-428.

Bibtex - Download

@article{4c2c88cc10fc41c39fd1ae43ebe61375,
title = "Macrophages in gene therapy: cellular delivery vehicles and in vivo targets",
abstract = "The appearance and activation of macrophages are thought to be rapid events in the development of many pathological lesions, including malignant tumors, atherosclerotic plaques, and arthritic joints. This has prompted recent attempts to use macrophages as novel cellular vehicles for gene therapy, in which macrophages are genetically modified ex vivo and then reintroduced into the body with the hope that a proportion will then home to the diseased site. Here, we critically review the efficacy of various gene transfer methods (viral, bacterial, protozoan, and various chemical and physical methods) in transfecting macrophages in vitro, and the results obtained when transfected macrophages are used as gene delivery vehicles. Finally, we discuss the use. of various viral and nonviral methods to transfer genes to macrophages in vivo. As will be seen, definitive evidence for the use of macrophages as gene transfer vehicles has yet to be provided and awaits detailed trafficking studies in vivo. Moreover, although methods for transfecting macrophages have improved considerably in efficiency in recent years, targeting of gene transfer specifically to macrophages in vivo remains a problem. However, possible solutions to this include Placing transgenes under the control of macrophage-specific promoters to limit expression to macrophages or stably transfecting CD34(+) precursors of monocytes-macrophages and then differentiating these cells into monocytes/macrophages ex vivo. The latter approach could conceivably lead to the bone marrow precursor cells of patients with inherited genetic disorders being permanently fortified or even replaced with genetically modified cells.",
keywords = "vector, adoptive immunotherapy, transfection, homing, transcriptional targeting, MONOCYTE-DERIVED MACROPHAGES, CHRONIC GRANULOMATOUS-DISEASE, HEMATOPOIETIC STEM-CELLS, TUMOR-NECROSIS-FACTOR, IN-VIVO, DENDRITIC CELLS, IFN-GAMMA, ADOPTIVE IMMUNOTHERAPY, KUPFFER CELLS, INTRAVENOUS-INJECTION",
author = "B Burke and S Sumner and N Maitland and Lewis, {C E}",
year = "2002",
month = "9",
language = "English",
volume = "72",
pages = "417--428",
journal = "Journal of leukocyte biology",
issn = "0741-5400",
publisher = "FASEB",
number = "3",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - Macrophages in gene therapy: cellular delivery vehicles and in vivo targets

AU - Burke, B

AU - Sumner, S

AU - Maitland, N

AU - Lewis, C E

PY - 2002/9

Y1 - 2002/9

N2 - The appearance and activation of macrophages are thought to be rapid events in the development of many pathological lesions, including malignant tumors, atherosclerotic plaques, and arthritic joints. This has prompted recent attempts to use macrophages as novel cellular vehicles for gene therapy, in which macrophages are genetically modified ex vivo and then reintroduced into the body with the hope that a proportion will then home to the diseased site. Here, we critically review the efficacy of various gene transfer methods (viral, bacterial, protozoan, and various chemical and physical methods) in transfecting macrophages in vitro, and the results obtained when transfected macrophages are used as gene delivery vehicles. Finally, we discuss the use. of various viral and nonviral methods to transfer genes to macrophages in vivo. As will be seen, definitive evidence for the use of macrophages as gene transfer vehicles has yet to be provided and awaits detailed trafficking studies in vivo. Moreover, although methods for transfecting macrophages have improved considerably in efficiency in recent years, targeting of gene transfer specifically to macrophages in vivo remains a problem. However, possible solutions to this include Placing transgenes under the control of macrophage-specific promoters to limit expression to macrophages or stably transfecting CD34(+) precursors of monocytes-macrophages and then differentiating these cells into monocytes/macrophages ex vivo. The latter approach could conceivably lead to the bone marrow precursor cells of patients with inherited genetic disorders being permanently fortified or even replaced with genetically modified cells.

AB - The appearance and activation of macrophages are thought to be rapid events in the development of many pathological lesions, including malignant tumors, atherosclerotic plaques, and arthritic joints. This has prompted recent attempts to use macrophages as novel cellular vehicles for gene therapy, in which macrophages are genetically modified ex vivo and then reintroduced into the body with the hope that a proportion will then home to the diseased site. Here, we critically review the efficacy of various gene transfer methods (viral, bacterial, protozoan, and various chemical and physical methods) in transfecting macrophages in vitro, and the results obtained when transfected macrophages are used as gene delivery vehicles. Finally, we discuss the use. of various viral and nonviral methods to transfer genes to macrophages in vivo. As will be seen, definitive evidence for the use of macrophages as gene transfer vehicles has yet to be provided and awaits detailed trafficking studies in vivo. Moreover, although methods for transfecting macrophages have improved considerably in efficiency in recent years, targeting of gene transfer specifically to macrophages in vivo remains a problem. However, possible solutions to this include Placing transgenes under the control of macrophage-specific promoters to limit expression to macrophages or stably transfecting CD34(+) precursors of monocytes-macrophages and then differentiating these cells into monocytes/macrophages ex vivo. The latter approach could conceivably lead to the bone marrow precursor cells of patients with inherited genetic disorders being permanently fortified or even replaced with genetically modified cells.

KW - vector

KW - adoptive immunotherapy

KW - transfection

KW - homing

KW - transcriptional targeting

KW - MONOCYTE-DERIVED MACROPHAGES

KW - CHRONIC GRANULOMATOUS-DISEASE

KW - HEMATOPOIETIC STEM-CELLS

KW - TUMOR-NECROSIS-FACTOR

KW - IN-VIVO

KW - DENDRITIC CELLS

KW - IFN-GAMMA

KW - ADOPTIVE IMMUNOTHERAPY

KW - KUPFFER CELLS

KW - INTRAVENOUS-INJECTION

M3 - Literature review

VL - 72

SP - 417

EP - 428

JO - Journal of leukocyte biology

JF - Journal of leukocyte biology

SN - 0741-5400

IS - 3

ER -