Recombinant oncolytic virus, preparation method therefor, use thereof and medicine thereof

An oncolytic virus, wherein the genome of the oncolytic virus contains the following exogenous elements:

• (1) a first expression cassette comprising a first promoter, a first interfering RNA expression sequence for expressing a first interfering RNA, and a second interfering RNA expression sequence for expressing a second interfering RNA;
• (2) a target sequence;
• and
• (3) a second expression cassette,
• wherein:
• the nucleotide sequence of the target sequence is the sequence set forth in SEQ ID NO:
• 1, the nucleotide sequence of the first interfering RNA is the sequence set forth in SEQ ID NO:
• 2, and the nucleotide sequence of the second interfering RNA is the sequence set forth in SEQ ID NO:
• 3;
• the first interfering RNA expression sequence is used to express the first interfering RNA which binds to the target sequence in a first cell, the first interfering RNA expression sequence being driven by the first promoter so as to express the first interfering RNA in the first cell;
• the target sequence is located at the 5′ or 3′ untranslated region (UTR) of an essential gene required for replication of the oncolytic virus;
• the second expression cassette comprises a second promoter and an inhibitory component expression sequence, wherein the inhibitory component expression sequence is used to express an inhibitory component which inhibits the biosynthesis and/or bioactivity of a first enzyme involved in the biosynthesis of interfering RNA, in a second cell, the inhibitory component expression sequence being driven by the second promoter so as to express the inhibitory component in the second cell, wherein the inhibitory component comprises a third interfering RNA which inhibits expression of a second enzyme involved in the biosynthesis of the first enzyme, wherein the nucleotide sequence of the third interfering RNA is the sequence set forth in SEQ ID NO:4;
• and
• the first and the second cells are different cell types.