Recombinant Sendai virus vectors for activated T lymphocytes.
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.
Okano
S
S
Division of Pathophygiological and Experimental Pathology, Department of Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Yonemitsu
Y
Y
Nagata
S
S
Sata
S
S
Onimaru
M
M
Nakagawa
K
K
Tomita
Y
Y
Kishihara
K
K
Hashimoto
S
S
Nakashima
Y
Y
Sugimachi
K
K
Hasegawa
M
M
Sueishi
K
K
D000818:Animals; D002460:Cell Line; D005260:Female; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics*; D049452:Green Fluorescent Proteins; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008164:Luminescent Proteins / Q000235:genetics; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism; D029082:Sendai virus / Q000235:genetics*; D013601:T-Lymphocytes / Q000378:metabolism*; D013997:Time Factors
D008164:Luminescent Proteins; D011948:Receptors, Antigen, T-Cell; D049452:Green Fluorescent Proteins