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Review
, 12 (5), 410-6

Development of Sendai Virus Vectors and Their Potential Applications in Gene Therapy and Regenerative Medicine

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Review

Development of Sendai Virus Vectors and Their Potential Applications in Gene Therapy and Regenerative Medicine

Mahito Nakanishi et al. Curr Gene Ther.

Abstract

Gene delivery/expression vectors have been used as fundamental technologies in gene therapy since the 1980s. These technologies are also being applied in regenerative medicine as tools to reprogram cell genomes to a pluripotent state and to other cell lineages. Rapid progress in these new research areas and expectations for their translation into clinical applications have facilitated the development of more sophisticated gene delivery/expression technologies. Since its isolation in 1953 in Japan, Sendai virus (SeV) has been widely used as a research tool in cell biology and in industry, but the application of SeV as a recombinant viral vector has been investigated only recently. Recombinant SeV vectors have various unique characteristics, such as low pathogenicity, powerful capacity for gene expression and a wide host range. In addition, the cytoplasmic gene expression mediated by this vector is advantageous for applications, in that chromosomal integration of exogenous genes can be undesirable. In this review, we introduce a brief historical background on the development of recombinant SeV vectors and describe their current applications in gene therapy. We also describe the application of SeV vectors in advanced nuclear reprogramming and introduce a defective and persistent SeV vector (SeVdp) optimized for such reprogramming.

Figures

Fig. (1)
Fig. (1)
Characteristics of Sendai virus. (a) Schematic structure of Sendai virus. Reprinted with the permission of Nikkei Science, Inc. (b) Cross-section view of Sendai virus examined with transmission electron microscopy (courtesy of Dr. Takao Senda, Fujita Health University School of Medicine). (c) Purified Sendai virus in a centrifuge tube. Sendai virus was propagated in 500 fertilized chicken eggs and was purified extensively by sucrose step centrifugation. The large off-white pellet contains about 500 mg of purified Sendai virus as protein.
Fig. (2)
Fig. (2)
Genome structure of the Sendai virus. Transcription of capped mRNAs starts from the transcription initiation signal with RNA-dependent RNA polymerase (L protein). Transcription ends at the transcription termination signal, followed by a poly-A signal.
Fig. (3)
Fig. (3)
Compatibility of two independent SeVdp vectors in a single cell. (Top) Structure of SeV vectors. cDNA sequences encoding for enhanced green fluorescent protein (EGFP) cDNA and Kusabira orange (KO) were installed on a single SeV vector SeVdp(KO/EGFP) (a) or on two SeV vectors SeVdp(KO) and SeVdp(EGFP) separately (b). (Middle) Fluorescence images of cells expressing KO and EGFP from these SeV vectors. Fluorescence microscopy images of KO and of EGFP were obtained separately with specific filter sets and merged after being converted to an artificial color output (green for EGFP and red for KO). Cells carry a single SeV vector SeVdp(KO/EGFP) (c) or mixture of two SeV vectors SeVdp(KO) and SeVdp(EGFP) (d). (Bottom) Expression levels of KO and EGFP were analyzed quantitatively using flow cytometry. The ratio of the signal intensities of EGFP and KO in each cell is shown as a histogram. Cells carry a single SeV vector SeVdp(KO/EGFP) (e) or mixture of two SeV vectors SeVdp(KO) and SeVdp(EGFP) (f). Reprinted from reference 26 with permission.
Fig. (4)
Fig. (4)
Genome structure of defective and persistent Sendai virus (SeVdp) vector. SeVdp has mutations in the L and P genes, which are responsible for low cytotoxicity and for defective induction of IFNβ. The M, F and HN genes are deleted and replaced with genes of interest (A–D). SeVdp-iPS was installed with Oct4, Sox2, Klf4 and c-Myc cDNAs on a single vector.

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