Journal of Nippon Medical School: Vol.71 No.1 page.051

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ArticleTitle Establishment of Modified Retroviral Vector Targeting X-Linked Severe Combined Immunodeficiency

AuthorList Cai Ling Zhi¹, Makoto Migita^1-3, Jun Hayakawa¹ and Yoshitaka Fukunaga¹

Affiliation ¹Department of Pediatrics, Nippon Medical School
²Department of Biochemistry and Molecular Biology, Nippon Medical School
³Division of Gene Therapy Research Center for Advanced Medical Technology, Nippon Medical School

Language EN

Volume 71

Issue 1

Year 2004

Page 51-56

Received April 8, 2003

Accepted October 17, 2003

Keywords Gene therapy, X-linked severe combined immunodeficiency, hematopoietic stem cells, retrovirus vector

Abstract Gene therapy targeting hematopoietic stem cells has been proposed as a potential therapy for numerous genetic disorders affecting hematopoiesis. Moloney murine leukemia retroviral vectors are now widely used for clinical gene transfer into hematopoietic progenitors and progeny. However, maintaining expression of therapeutic genes inserted via moloney murine leukemia virus (MoMLV)-based vectors has proven to be more difficult than previously expected. In this study, an MND-IL-2R vector containing IL-2RcγcDNA to treat X-linked severe combined immunodeficiency (X-SCID) was constructed from an MND vector that was modified by substituting the myeloproliferative sarcoma virus (MPSV) enhancer for that of MoMLV, deleting the negative control region located in the long terminal repeat (LTR) as an enhancer, and replacing the primer binding site (PBS) of MoMLV with the PBS of the endogenous murine retrovirus dl587rev. This vector was transduced into human CD34+progenitor cells with comparable efficiency to that of the MoMLV-based vector. The use of this newly created vector may be advantageous for gene therapy of X-SCID.

Correspondence to Correspondence to Makoto Migita MD, Ph D, Department of Pediatrics, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan
Migita-Makoto-bmb@nms.ac.jp

ArticleTitle	Establishment of Modified Retroviral Vector Targeting X-Linked Severe Combined Immunodeficiency
AuthorList	Cai Ling Zhi¹, Makoto Migita^1-3, Jun Hayakawa¹ and Yoshitaka Fukunaga¹
Affiliation	¹Department of Pediatrics, Nippon Medical School ²Department of Biochemistry and Molecular Biology, Nippon Medical School ³Division of Gene Therapy Research Center for Advanced Medical Technology, Nippon Medical School
Language	EN
Volume	71
Issue	1
Year	2004
Page	51-56
Received	April 8, 2003
Accepted	October 17, 2003
Keywords	Gene therapy, X-linked severe combined immunodeficiency, hematopoietic stem cells, retrovirus vector
Abstract	Gene therapy targeting hematopoietic stem cells has been proposed as a potential therapy for numerous genetic disorders affecting hematopoiesis. Moloney murine leukemia retroviral vectors are now widely used for clinical gene transfer into hematopoietic progenitors and progeny. However, maintaining expression of therapeutic genes inserted via moloney murine leukemia virus (MoMLV)-based vectors has proven to be more difficult than previously expected. In this study, an MND-IL-2R vector containing IL-2RcγcDNA to treat X-linked severe combined immunodeficiency (X-SCID) was constructed from an MND vector that was modified by substituting the myeloproliferative sarcoma virus (MPSV) enhancer for that of MoMLV, deleting the negative control region located in the long terminal repeat (LTR) as an enhancer, and replacing the primer binding site (PBS) of MoMLV with the PBS of the endogenous murine retrovirus dl587rev. This vector was transduced into human CD34+progenitor cells with comparable efficiency to that of the MoMLV-based vector. The use of this newly created vector may be advantageous for gene therapy of X-SCID.
Correspondence to	Correspondence to Makoto Migita MD, Ph D, Department of Pediatrics, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan Migita-Makoto-bmb@nms.ac.jp