Naked Sendai virus vector lacking all of the envelope‐related genes: reduced cytopathogenicity and immunogenicity

Abstract

The deletion of genes from the SeV genome and the additional mutation are very effective for reducing both the immunogenic and cytopathic reactions to the SeV vector. These modifications are expected to improve the safety and broaden the range of clinical applications of this new class of cytoplasmic RNA vector.

Impact of deletion of envelope-related genes of recombinant Sendai viruses on immune responses following pulmonary gene transfer of neonatal mice

“…18 rSeV/dFdMdHN is the further advanced design without any envelope-related genes in the vector genome. 19,20 These rSeVs were titrated by assessing CIU (cell infectivity units). [18][19][20] Role of SeV-envelope-related genes on host immune response S Tanaka et al The survival curves of these mice are also shown.…”

“…19,20 These rSeVs were titrated by assessing CIU (cell infectivity units). [18][19][20] Role of SeV-envelope-related genes on host immune response S Tanaka et al The survival curves of these mice are also shown. The curves were analyzed using Kaplan-Mayer's method.…”

“…Insertion of temperature-sensitive mutations into the genome template of rSeV and the recovery procedures of F-deficient SeV vectors from cDNAs were described previously. [18][19][20] Briefly, approximately 10 7 LLC-MK2 cells were transfected with template pSeV and pCAG-plasmids each carrying the NP, P, M, F, HN, or L gene. 20 The cells were maintained in MEM containing trypsin, and 24 h later, they were overlaid with LLC-MK2/F7/M#33/HN7 cells after induction of M, F and HN proteins by AxCANCre infection at an MOI of five and cultured for another 48 h. The cell lysate was infected into new LLC-MK2/F7/ M#33/HN7 cells after AxCANCre infection.…”

“…17 To overcome these limitations, we recently produced two new types of rSeV/dF ( Figure 1); namely, a temperature-sensitive mutant rSeV/dF (ts-rSeV/dF) 18,19 and an rSeV lacking all three envelope-related genes, F, M and HN (rSeV/dFdMdHN). 20 Since a reduction in the number of vector-related proteins may alter hostimmune responses, as suggested in our recent study, 20 we here examined the efficacy of these two vector constructs for pulmonary gene transfer. We assessed innate-(natural killer cell (NK cell) activity and proinflammatory cytokine production) and acquired-(cytotoxic T-lymphocytes (CTL) activity and antibody production) immunity-related events following pulmonary gene transfer in neonatal and young adult mice.…”

Generation of optimized and urokinase-targeted oncolytic Sendai virus vectors applicable for various human malignancies

“…3 Using sophisticated manipulating technology of the genome of SeV, namely 'Reverse Genetics, ' we recently generated SeV vectors lacking envelope-related genes, including fusion (F) gene-deleted (SeV/DF), 4 matrix (M) gene-deleted (SeV/DM), 5 hemagglutinin/neuraminidase (HN) gene-deleted (SeV/DHN), both M and F genesdeleted (SeV/DMDF) 6 and all of the envelope-related genes-deleted (SeV/DMDFDHN). 7 Among the proteins contained in the viral lipid bilayer, M protein plays a central role in secondary virus assembly and budding from infected cells. Therefore, deletion of the M gene from SeV almost completely abolished virus maturation during formation of infectious particles in infected cells and instead caused cell-to-cell vector spreading through membrane fusion, forming large syncytia and resulting in cell death by the active F protein under supplementation of trypsin.…”