Nipah virus envelope pseudotyped lentiviruses and methods of their use
AssigneeThe Regents of the University of California
InventorsBenhur Lee, Karina Palomares, Olivier Pernet
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Abstract
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 glyocproteins 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.
Claims13
-11. (canceled)
A method for specifically targeting a desired nucleic acid to ephrin B2 expressing cells, the method comprising contacting a Nipah virus (NiV) envelope pseudotyped lentivirus particle with ephrin B2 expressing cells, or administering the NiV pseudotyped lentivirus particle to a subject organism possessing ephrin B2 expressing cells,
- wherein the NiV pseudotyped lentivirus particle comprises 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 or a truncated Niv-G selected from the group consisting of the amino acid SEQ ID NOS:
- 13, 15, 17, 19, 21 and 23,
- wherein the lentivirus infects cells expressing Ephrin B2 or Ephrin B3 receptors;
- and
- wherein the pseudotyped lentivirus particle further comprises the desired nucleic acid.
A method for delivering a desired nucleic acid across crossing the blood brain barrier, the method comprising administering to a subject organism a NiV pseudotyped lentivirus particle,
- wherein the NiV pseudotyped lentivirus particle comprises 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 or a truncated Niv-G selected from the group consisting of the amino acid SEQ ID NOS:
- 13, 15, 17, 19, 21 and 23,
- wherein the lentivirus infects cells expressing Ephrin B2 or Ephrin B3 receptors;
- and
- wherein the pseudotyped lentivirus particle further comprises the desired nucleic acid.
A method for altering brain function in a subject, the method comprising injecting a NiV pseudotyped lentivirus particle into specific areas of said subject's brain,
- wherein the NiV pseudotyped lentivirus particle comprises 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 or a truncated Niv-G selected from the group consisting of the amino acid SEQ ID NOS:
- 13, 15, 17, 19, 21 and 23,
- wherein the lentivirus infects cells expressing Ephrin B2 or Ephrin B3 receptors;
- and
- wherein the pseudotyped lentivirus further comprises a desired nucleic acid effective for altering brain function.
Dependencies are inferred from the claim text.