1. ¹Division of Molecular Therapy, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
2. ²Department of Virology and Preventive Medicine, Gunma University School of Medicine, Maebashi, Japan
3. ³Age Dimension Team, Age Dimension Research Center, National Institute of Advanced Industrial Science and Technology, Tsukuba, Japan
4. ⁴Department of Immunology, Institute of Basic Medical Science, University of Tsukuba, Tsukuba, Japan
5. ⁵Division of Molecular and Clinical Genetics, Department of Molecular Genetics, Medical Institute of Bioregulation, Kyushu University, Beppu, Japan

Correspondence: Dr Y Soda, Division of Molecular Therapy, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan

⁶Current address: Technology and Development Team for Biosignal Program, Bioresource Center, The Institute of Physical and Chemical Research, Tsakuba, Japan

⁷The first two authors equally contributed to this work

Received 23 August 2002; Accepted 7 February 2003.

Abstract

Difficulty in gene transduction of human blood cells, including hematopoietic stem cells, has hampered the development of gene therapy applications for hematological disorders, encouraging the development and use of new gene delivery systems. In this study, we used a third-generation self-inactivating (SIN) lentiviral vector system based on human immunodeficiency virus type 1 (HIV-1) to improve transduction efficiency and prevent vector-related toxicity. The transduction efficiency of the HIV-1-based vector was compared directly with the Moloney murine leukemia virus (MLV) SIN vector in human leukemia cell lines. Initial transduction efficiencies were almost 100% for the HIV and less than 50% for the MLV vectors. Similar results were observed in 11 types of primary cells obtained from leukemia or myeloma patients. Transgene expression persisted for 8 weeks in cells transduced with the HIV vector, but declined with the MLV vector. In addition, resting peripheral blood lymphocytes and CD34⁺ hematopoietic cells were transduced successfully with the HIV vector, but not with the MLV vector. Finally, we confirmed vector gene integration in almost all colony-forming cells transduced with the HIV vector, but not with the MLV vector. In conclusion, this lentiviral vector is an excellent gene transduction system for human blood cells because of its high gene transduction and host chromosome integration efficiency.