Recombinant Sendai virus vectors deleted in both the matrix and the fusion genes: efficient gene transfer with preferable properties
✍ Scribed by Makoto Inoue; Yumiko Tokusumi; Hiroshi Ban; Masayuki Shirakura; Takumi Kanaya; Mariko Yoshizaki; Takashi Hironaka; Yoshiyuki Nagai; Akihiro Iida; Mamoru Hasegawa
- Book ID
- 102337587
- Publisher
- John Wiley and Sons
- Year
- 2004
- Tongue
- English
- Weight
- 408 KB
- Volume
- 6
- Category
- Article
- ISSN
- 1099-498X
- DOI
- 10.1002/jgm.597
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✦ Synopsis
Abstract
Background
Sendai virus (SeV) is a new type of cytoplasmic RNA vector, which infects and replicates in most mammalian cells, directs high‐level expression of the genes on its genome and is free from genotoxicity. In order to improve this vector, both the matrix (M) and fusion (F) genes were deleted from its genome.
Methods
For the recovery of the M and F genes‐deleted SeV (SeV/ΔMΔF), the packaging cell line was established by using a Cre/loxP induction system. SeV/ΔMΔF was characterized and compared with wild‐type and F or M gene‐deleted SeV vectors in terms of transduction ability, particle formation, transmissible property and cytotoxicity.
Results
SeV/ΔMΔF was propagated in high titers from the packaging cell line. When this vector was administered into the lateral ventricle and the respiratory tissue, many of the ependymal and epithelial cells were transduced, respectively, as in the case of wild‐type SeV. F gene‐deletion made the SeV vector non‐transmissible, and M gene‐deletion worked well to inhibit formation of the particles from infected cells. Simultaneous deletions of these two genes in the same genome resulted in combining both advantages. That is, both virus maturation into particles and transmissible property were almost completely abolished in cells infected with SeV/ΔMΔF. Further, the cytopathic effect of SeV/ΔMΔF was significantly attenuated rather than that of wild type in vitro and in vivo.
Conclusions
SeV/ΔMΔF is an advanced type of cytoplasmic RNA vector, which retains efficient gene transfer, gains non‐transmissible properties and loses particle formation with less cytopathic effect. Copyright © 2004 John Wiley & Sons, Ltd.