Sendai virus (SeV) is an enveloped virus possessing a nonsegmented negative sense RNA genome and is a member of the family Paramyxoviridae in the superfamily Mononegavirales. By the end of 1980s, genome nucleotide sequences were determined for the representative members of Mononegavirales including SeV. The common task of next challenge was to recover infectious virus entirely from cDNA since manipulation of viral genome at will (reverse genetics) was essential to verify information and theories obtained by conventional methodology such as forward genetics and to settle outstanding questions that cannot be addressed by conventional virology. There was keen competition over many years in the mid-1990s to be the first and to be the best in establishing reverse genetics. In 1996, we succeeded in generating the system for SeV. As a result of making the best use of inventiveness our SeV recovery efficiency from cDNA was about 100 times higher compared with those for other members of Mononegavirales, thus facilitating to verify classic theories and resolve many unsettled questions in viral replication and pathogenesis in this superfamily.
　　The SeV gene expression was quite robust. The virus fulfils its lifecycle entirely in the cytoplasm and does not have a nuclear phase nor undergo chromosomal integration, indicating that it causes theoretically no genotoxicity including oncogenesis. Besides, no link of SeV to any human diseases has been described so far. It is just a mouse pathogen causing pneumonia. These features prompted us to use SeV as a novel class of expression vector to deliver a gene of interest such as therapeutic and vaccine antigen genes. Indeed, the expression level of a foreign gene inserted into SeV genome was extremely high. To further substantiate the safety, we created infectious but none-transmissible SeV vectors by deleting one or more Sendai viral transmission-responsible genes. Remarkable products have been manufactured, some of which were already marketed or are about to be marketed.
　 　Yamanaka’s four reprogramming factors were inserted into and expressed from a combination of SeVs with various temperature sensitive mutations in the viral RNA polymerase genes. This kit (named CytoTune iPS) efficiently generated human iPSCs (induced pluripotent stem cells) and moreover, after fulfilling the jobs, the four factors and SeVs were erased. Thus this system generates “footprint free” iPSCs. SeV expressing the basic fibroblast growth factor not only caused no severe adverse events but also displayed remarkable therapeutic effect on limb ischemia (also known as peripheral artery disease), when intramuscularly injected into the spots surrounding the diseased leg arteries. For cell to cell spreading, SeV needs a host-cellular trypsin-like protease that proteolytically activates the viral fusion glycoprotein required for virus entry to cells. The cleavage site was converted to those susceptible to matrix metalloprotease or urokinase type plasminogen activator (uPA), both of which are known to be overexpressed in malignant tumor tissues. These protease-activation mutants indeed suppressed selectively the growth of tumors transplanted into animals. uPA activating virus was found to be efficacious on a broad range of tumor cell lines and named BioKnife to resect malignant tumor tissues. SeV vectors expressing vaccine antigen genes of infectious diseases were constructed and are currently under testing not only at the animal level but in humans. There are some more attempts to expand the potential of SeV technology
　　Our SeV study over the past 20 years thus is comparable to a journey from a mouse pathogen to the innovation of a novel class of non-genotoxic, multipurpose expression vector with extremely high performance. We very much hope that this keynote speech will touch off sharing the SeV platform with Formosan biologists and physicians.