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.
Claims17
A method for specifically targeting a desired nucleic acid, the method comprising contacting a Nipah virus (NiV) envelope pseudotyped lentivirus particle with ephrin B2 expressing cells in vitro, or systemically administering a therapeutically effective amount of the NiV pseudotyped lentivirus particle to a subject in need thereof to target cells expressing ephrin B2 or ephrin B3,
- 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 to lung, heart, spleen and/or liver, the method comprising systemically administering to a subject a therapeutically effective amount of 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 therapeutically effective amount of a NiV pseudotyped lentivirus particle into specific areas of said subject's brain, wherein the NiV pseudotyped lentivirus particle transduces Nestin+ neural stem 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 further comprises a desired nucleic acid effective for altering brain function.
A method for delivering a desired nucleic acid across the blood-brain barrier, the method comprising systemically administering to a subject a therapeutically effective amount of 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 endothelial cells expressing Ephrin B2 or over-expressing ephrin B2 and transcytoses across the blood-brain barrier
- wherein the pseudotyped lentivirus particle further comprises the desired nucleic acid.
Dependencies are inferred from the claim text.