Rift Valley fever virus (RVFV), which belongs to family Bunyaviridae, genus Phlebovirus, circulates between mosquitoes and ruminants in sub-Saharan African countries, and causes abortion and fetal malformation in pregnant ewes or other ruminants. RVFV outbreaks among humans and ruminants have been reported in several African countries and Arabian Peninsula. Some human patients develop hemorrhagic fever, encephalitis or blindness after temporal febrile period. RVFV is listed as Category A pathogen, and overlap select agent by CDC/USDA. Vaccination is the only effective method to contain the spread of RVFV, yet there are no licensed vaccines available for general public. RVFV has tripartite negative-stranded genomic RNA named S, M and L-segments. NSs protein encoded in S-segment is known to be a major virulence factor, and inhibits cellular general transcription by inhibiting transcription factor IIH, inhibits the activation of interferon-β gene promoter, and promotes the degradation of dsRNA-dependent protein kinase (PKR). A candidate live-attenuated vaccine, MP-12 strain has been generated by serial 12 times passages of Egyptian wild-type isolate, ZH548 strain, in MRC-5 cells in the presence of chemical mutagen 5-fluorouracil. MP-12 encodes several mutations in M and L-segments, yet MP-12 encodes functional NSs protein. MP-12 is proven to be highly immunogenic in ruminants and human volunteers, yet there are still some safety concerns to be addressed. Our laboratory uses a well-established reverse genetics system for RVFV MP-12, and currently screens various MP-12 NSs mutants to identify a highly immunogenic vaccine candidate with attenuated NSs gene. We are also studying on the attenuation mechanism of MP-12 strain.