Retrovirus-like particles made non-infectious by a plurality of mutations
AssigneeSanofi Pasteur Limited
InventorsBenjamin Rovinski, Shi-Xian Cao, Fei-Long Yao, Roy Persson, Michel H. Klein
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Abstract
Non-infectious, retrovirus-like particles contain mutations to reduce gag-dependent RNA-packaging of the gag gene product, eliminate reverse transcriptase activity of the pol gene product, eliminate integrase activity of the pol gene product and eliminate RNase H activity of the pol gene product through genetic manipulation of the gag and pol genes. The corresponding nucleic acid molecules are described. The non-infectious, retrovirus-like particles have utility in in vivo administration including to humans and in diagnosis.
Claims63
A non-infectious, immunogenic, retrovirus-like particle comprising, in an assembly, gag, pol and env gene products, wherein at least one modification has been made to the pol and/or gag gene product, to effect at least one of the following:
- (a) reduce gag-dependent RNA packaging of the gag gene product;
- (b) substantially eliminate reverse transcriptase activity of the pol gene product;
- (c) substantially eliminate integrase activity of the pol gene product;
- and
- (d) substantially eliminate RNase H activity of the pol gene product.
A nucleic acid molecule, comprising a modified retroviral genome from which long terminal repeats are absent and containing gag, pol and env genes in their natural genomic arrangement and means for expression operatively connected to said modified retroviral genome for production of gene products in cells to produce non-infectious, immunogenic, retrovirus-like particles comprising an assembly of gag, pol and env gene products, wherein at least one codon in the gag or pol gene has been mutated to effect at least one of the following:
- (a) reduce gag-dependent RNA packaging activity of the gag gene product;
- (b) substantially eliminate reverse transcriptase activity of the pol gene products;
- (c) substantially eliminate integrase activity of the pol gene product;
- and
- (d) substantially eliminate RNase H activity of the pol gene product.
Dependencies are inferred from the claim text.