Attenuation of negative stranded RNA viruses by rearrangement of

Chemistry: molecular biology and microbiology – Virus or bacteriophage – except for viral vector or... – Inactivation or attenuation; producing viral subunits

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4242241, C12N 704, A61K 39205

Patent

active

061365858

ABSTRACT:
Provided is a method of attenuating a virus of the order Mononegavirales, comprising the step of: rearranging said virus' gene order by moving a gene essential for RNA replication away from its wild-type 3' promoter proximal position site, wherein said gene is an essential limiting factor for genome replication and is placed in the next to last position in the gene order. Also provided is a method of making an attenuated virus useful for a vaccine, comprising the steps of: rearranging said virus' gene order by moving a gene essential for RNA replication away from its wild-type 3' promoter proximal position site, wherein a gene which is a n essential limiting factor for genome replication is placed in the next to last position in the gene order; and placing a gene coding for an immune response inducing antigen in the position closest to the 3' end of the gene order. Also provided is a method of attenuating a virus of the order Mononegavirales, comprising the step of: rearranging said virus' gene order.

REFERENCES:
Wertz et al., Gene rearrangement attenuates expression and lethality of a nonsegmented negative strand RNA virus. Proc. Natl. Acad. Sci. USA 95(7):3501-3506, 1998.

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