Recombinant Sendai virus vectors for activated T lymphocytes

• Published in: Gene therapy Vol. 10; no. 16; pp. 1381 - 1391
• Main Authors: OKANO, S, YONEMITSU, Y, SUGIMACHI, K, HASEGAWA, M, SUEISHI, K, NAGATA, S, SATA, S, ONIMARU, M, NAKAGAWA, K, TOMITA, Y, KISHIHARA, K, HASHIMOTO, S, NAKASHIMA, Y
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01.08.2003
• Subjects: Animals; Antigens; Biological and medical sciences; Care and treatment; Cell activation; Cell Line; Centrifugation; Cytoplasm; Expression vectors; Female; Fundamental and applied biological sciences. Psychology; Gene Expression; Gene therapy; Genetic aspects; Genetic Therapy - methods; Genetic Vectors - administration & dosage; Genetic Vectors - genetics; Green fluorescent protein; Green Fluorescent Proteins; Health aspects; Humans; Immunologic diseases; Immunotherapy, Adoptive - methods; Luminescent Proteins - genetics; Lymphocyte Activation; Lymphocytes; Lymphocytes T; Methods; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Transgenic; Molecular and cellular biology; Physiological aspects; Polybrene; Protamine sulfate; Receptors, Antigen, T-Cell - genetics; Receptors, Antigen, T-Cell - metabolism; Sendai virus - genetics; T cells; T-Lymphocytes - metabolism; Time Factors; Canada; Japan; Genetics; gene therapy; Sendai virus vector; enhanced green fluorescent protein gene; T cells
• ISSN: 0969-7128; 1476-5462
• DOI: 10.1038/sj.gt.3301998

T-lymphocyte-directed gene therapy has potential as a treatment of subjects with immunological disorders. One current limitation of this therapeutic strategy is low gene transfer efficiency, even when complex procedures are used. We report herein that a recombinant Sendai virus vector (SeV) was able to overcome this issue. Using jellyfish enhanced green fluorescent protein gene (EGFP), we found that SeV was able to transduce and express a foreign gene specifically and efficiently in activated murine and human T cells, but not in naive T cells, without centrifugation or reagents including polybrene and protamine sulfate; the present findings were in clear contrast to those demonstrated with the use of retroviruses. The transduction was selective in antigen-activated T cells, while antigen-irrelevant T cells were not transduced, even under bystander activation from specific T-cell responses by antigens ex vivo. Receptor saturation studies suggested a possible mechanism of activated T-cell-specific gene transfer, ie, SeV might attach to naive T cells but might be unable to enter their cytoplasm. We therefore propose that the SeV vector system may prove to be a potentially important alternative in the area of T-cell-directed gene therapy used in the clinical setting.