Stable envelope proteins for retroviral, viral and liposome vectors and use in gene drug therapy

An isolated nucleic acid encoding a mutant retrovirus envelope protein comprising the substitution of one or more amino acids in at least one motif of the seven motifs listed in Table I, wherein said mutant protein allows for decreased shedding of the surface protein by increasing envelope stability and for increased fusion of retroviruses with cell membranes, while maintaining mutant envelope protein incorporation into a virion.

A nucleic acid encoding a mutant retroviral protein comprising at least one substitution of one or more amino acids, wherein said substitution of one or more amino acids corresponds to at least one mutation of at least one residue in alignment with 8His, 11Tyr, 16Glu, 24Thr, 35Trp, 38Trp, 102Arg, 104Lys, 107Glu, 108Thr, 109Thr, 121Gly, 123His, 124Arg, 128Ser, 132Gly, 133Gly, 134Pro, 135Asp, 136Ser, 137Phe, 138Tyr, 141Tyr, 142Trp, 151Tyr, 152Trp, 158Trp, 160Tyr, 196Val, 197Thr, 198Ser, 201Thr, 203His, 208Arg, 210Tyr, 217Gly, 223Arg, 224Leu, 225Arg, 226Tyr, 227Gln, 228Asn, 233Val, 235Ile, 240Val, 241Leu, and/or 243Asp of SEQ ID NO:

• 2.

A nucleic acid encoding a mutant retroviral protein comprising one or more amino acid substitutions, wherein said one or more substitutions at residues 8His, 11Tyr, 16Glu, 24Thr, 35Trp, 38Trp, 102Arg, 104Lys, 107Glu, 108Thr, 109Thr, 121Gly, 123His, 124Arg, 128Ser, 132Gly, 133Gly, 134Pro, 135Asp, 136Ser, 137Phe, 138Tyr, 141Tyr, 142Trp, 151Tyr, 152Trp, 158Trp, 160Tyr, 196Val, 197Thr, 198Ser, 201Thr, 203His, 208Arg, 210Tyr, 217Gly, 223Arg, 224Leu, 225Arg, 226Tyr, 227Gln, 228Asn, 233Val, 235Ile, 240Val, 241Leu, or 243Asp as set forth in SEQ ID NO:

• 2, and wherein said mutant protein allows for decreased shedding of the surface protein by suppressing precursor cleavage or increased envelope stability and fusion of retroviruses with cell membranes when said protein is expressed on the surface of a retroviral particle.

An isolated nucleic acid encoding a mutant retrovirus envelope protein comprising the substitution of one or more amino acids in at least one motif of the receptor binding domain, wherein said mutant protein allows for decreased shedding of the surface protein by suppressing precursor cleavage, while maintaining mutant envelope protein incorporation into a virion.

An isolated nucleic acid encoding a mutant retrovirus envelope protein comprising the substitution of one or more amino acids in at least one motif of the receptor binding domain, wherein said mutant protein allows for decreased shedding of the surface protein by increasing envelope protein stability and for increased envelope stability and fusion of retroviruses with cell membranes, while maintaining mutant envelope protein incorporation into a virion.

A nucleic acid encoding a mutant retroviral protein comprising one or more amino acid substitutions, wherein said one or more substitutions at residues 8His, 11Tyr, 16Glu, 24Thr, 35Trp, 38Trp, 102Arg, 104Lys, 107Glu, 108Thr, 109Thr, 121Gly, 123His, 124Arg, 128Ser, 132Gly, 133Gly, 134Pro, 135Asp, 136Ser, 137Phe;

• 138Tyr, 141Tyr, 142Trp, 151Tyr, 152Trp, 158Trp, 160Tyr, 196Val, 197Thr, 198Ser, 201Thr, 203His, 208Arg, 210Tyr, 217Gly, 223Arg, 224Leu, 225Arg, 226Tyr, 227Gln, 228Asn, 233Val, 235Ile, 240Val, 241Leu, or 243Asp asset forth in SEQ ID NO:
• 2, and wherein said mutant protein allows for decreased shedding of the surface protein by suppressing precursor cleavage or increased envelope stability and fusion of retroviruses with cell membranes when said protein is expressed on the surface of a retroviral particle.