Patent ID: 6080408
Filing Date: 2000-06-27
Classification: A61K,A61P,C07K,C12N

Abstract:
A nucleic acid molecule, comprising:a modified human immunodeficiency virus (HIV) genome, deficient in long terminal repeats (LTRs), containing the gag, pol and env genes in their natural genomic arrangement and means for expression operatively connected to said modified HIV genome for production of gene products in cells to produce non-infectious, immunogenic, non-replicating HIV retrovirus-like particles comprising, in an assembly, the gag, pot and env gene products, wherein:(1) at least one codon in the gag gene has been mutated to effect modification to the gag gene product in the first Cys-His box only of the gag gene product by replacing at least one amino acid residue in the first Cys-His box contributing to gag-dependent genomic viral RNA packaging into said HIV retrovirus-like particles to effect reduction of gag-dependent genomic viral RNA packaging into the particles while retaining the immunogenicity of the HIV retrovirus-like particles;(2) codons in the pol gene encoding a portion of the pol gene product contributing to reverse transcriptase activity have been deleted to substantially eliminate reverse transcriptase activity of the pol gene product in the HIV retrovirus-like particles;(3) codons in the pol gene encoding a portion of the pol gene product contributing to integrase activity have been deleted to substantially eliminate integrase activity of the pol gene product in the HIV retrovirus-like particles; and(4) codons in the pol gene encoding a portion of the pol gene product contributing to RNase H activity have been deleted to substantially eliminate RNase H activity of the pol gene product in the HIV retrovirus-like particles.