Nipah virus envelope pseudotyped lentiviruses and methods of their use
The present invention relates to lentiviral particles which have been pseudotyped with Nipah virus (NiV) fusion (F) and attachment (G) glycoproteins (NiVpp-F/G). Additionally, the present invention relates to truncated NiV-F glycoproteins useful in producing such NiVpp lentiviral particles, as well as to additional variant peptides which enhance activity. Further, the present invention relates to methods of using such lentiviral particles or sequences, for example in the treatment of cancer or CNS disorders.
1. A Nipah virus (NiV) envelope pseudotyped lentivirus particle comprising NiV fusion (NiV-F) and attachment (NiV-G) glycoproteins, wherein the NiV-F glycoprotein has a cytoplasmic tail truncation consisting of deletion of amino acid residues 525-544 of SEQ ID NO: 1 NiV-F (T234 truncation) and a mutation to an N-linked glycosylation site, wherein the Niv-G glycoprotein is a wild type Niv-G, and wherein the lentivirus infects cells expressing Ephrin B2 or Ephrin B3 receptors.
2. The Nipah virus envelope pseudotyped lentivirus of claim 1 , wherein the mutation to an N-linked glycosylation site comprises a substitution of glutamine for asparagine at amino acid position 99 of SEQ ID NO: 1 (DeltaN3 mutation).
3. A Nipah virus envelope pseudotyped lentivirus particle comprising NiV-F and NiV-G glycoproteins, wherein the NiV-F glycoprotein comprises a cytoplasmic tail truncation and a mutation to an N-linked glycosylation site and wherein the cytoplasmic tail truncation consists of deletion of amino acid residues 525-544 of SEQ ID NO: 1 NiV-F (T234 truncation), the mutation to an N-linked glycosylation site comprises a DeltaN3 mutation, and wherein the NiV-G glycoprotein is a wild type Niv-G or a truncated Niv-G selected from the group consisting of the amino acid SEQ ID NOS: 13, 15, 17, 19, 21 and 23, and wherein the lentivirus infects cells expressing Ephrin B2 or Ephrin B3 receptors.
4. The Nipah virus envelope pseudotyped lentivirus of claim 1 , which exhibits about 100-fold increased viral transduction titers relative to wild type Niv-F Nipah virus envelope pseudotyped lentivirus.
5. A method for delivering a desired nucleic acid to cells which express Ephrin B2 or Ephrin B3, the method comprising contacting cells in vitro with the pseudotyped lentivirus of claim 1 or claim 3 , wherein the pseudotyped lentivirus further comprises a transfer vector comprising the desired nucleic acid.