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Recombinant Sendai virus‐mediated gene transfer to vasculature: a new class of efficient gene transfer vector to the vascular system
Author(s) -
Masaki Ichiro,
Yonemitsu Yoshikazu,
Komori Kimihiro,
Ueno Hikaru,
Nakashima Yutaka,
Nakagawa Kazunori,
Fukumura Masayuki,
Kato Atsushi,
Hasan Mohammad K.,
Nagai Yoshiyuki,
Sugimachi Keizo,
Hasegawa Mamoru,
Sueishi Katsuo
Publication year - 2001
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.00-0460fje
Subject(s) - sendai virus , gene transfer , vector (molecular biology) , adeno associated virus , gene , genetic enhancement , viral vector , recombinant dna , virus , virology , biology , restenosis , computational biology , genetics , medicine , surgery , stent
ABSTRACT Unsolved issues in clinical gene therapy for cardiovascular diseases include gene transfer efficiency and the requirement of a longer exposure time. We developed a novel mononegavirus vector, recombinant Sendai virus (SeV), and tested whether it can overcome the present hurdles. SeV showed dose‐dependent and persistent gene expression in either proliferating or arrested cells, suggesting stability of RNA genome of the vector. An outstanding feature of the SeV‐mediated gene transfer was that even a brief exposure provided nearly peak gene expression in both culture cells and human veins ex vivo, as well as rabbit carotid arteries in vivo. Gene transfer to human great saphenous veins showed high efficacy in luminal and vasa vasoral endothelial cells and in adventitial fibroblasts via both intraluminal delivery and simple floating; however, only scattered cells were transfected in both neointima and media, regardless of the infusion pressure. Veins with a dissected neointima showed a clear transfection to medial cells, suggesting that the barrier in neointima reduces SeV‐mediated gene transfer to tunica media, similar to the case with adenoviruses. Although the fibromuscular neointima is a common obstacle, these findings suggest that SeV may overcome other limitations of current vectors. SeV may be an important new vector in treating subjects with vascular disorders.