US2023285591A1PendingUtilityA1

Nipah virus envelope pseudotyped lentiviruses and methods of their use

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Assignee: UNIV CALIFORNIAPriority: Mar 26, 2012Filed: Jan 6, 2023Published: Sep 14, 2023
Est. expiryMar 26, 2032(~5.7 yrs left)· nominal 20-yr term from priority
Inventors:Benhur LeeKarina PalomaresOlivier Pernet
C12N 7/00A61K 48/0008C12N 15/86C12N 2740/15043C12N 2760/18222C12N 2810/6027A61K 39/12C12N 2760/18234C12N 2740/15041C12N 2760/18232C12N 2760/18245A61P 35/00A61K 48/00C12N 2740/15032C12N 2760/18241A61K 48/0075C12N 2740/15021C12N 2740/15071C12N 2760/18271C12N 2810/6072
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Claims

Abstract

The present invention realtes 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 treatetment of cancer or CNS disorders.

Claims

exact text as granted — not AI-modified
What is claimed is: 
     
         1 - 11 . (canceled) 
     
     
         12 . A method of delivering a nucleic acid to a cell, the method comprising contacting a Nipah virus (NiV) envelope pseudotyped lentivirus particle comprising a nucleic acid for delivery with cells,
 wherein the NiV pseudotyped lentivirus particle comprises Nipah Virus fusion (NiV-F) and Nipah Virus attachment (NiV-G) proteins,   wherein the NiV-F protein comprises a deletion in its cytoplasmic tail relative to a wild type NiV-F sequence, wherein the NiV-F protein comprises a cytoplasmic tail lacking amino residues 525-546 of SEQ ID NO: 1,   wherein the NiV-G protein is wild-type NiV-G or is a NiV-G protein that has a cytoplasmic tail truncation comprising a deletion in its cytoplasmic tail relative to wild type NiV-G sequence,   and wherein the NiV envelope pseudotyped lentivirus particle has increased viral transduction titer compared to a lentivirus particle pseudotyped with wild-type NiV-F and wild-type NiV-G.   
     
     
         13 . The method of  claim 12 , wherein the contacting is in vitro. 
     
     
         14 . The method of  claim 12 , wherein the contacting is in vivo. 
     
     
         15 . A method of delivering a nucleic acid to a cell, the method comprising administering a therapeutically effective amount of a NiV pseudotyped lentivirus particle comprising a nucleic acid for delivery to a subject,
 wherein the NiV pseudotyped lentivirus particle comprises Nipah Virus fusion (NiV-F) and Nipah Virus attachment (NiV-G) proteins,   wherein the NiV-F protein comprises a deletion in its cytoplasmic tail relative to a wild type NiV-F sequence, wherein the NiV-F protein comprises a cytoplasmic tail lacking amino residues 525-546 of SEQ ID NO: 1,   wherein the NiV-G protein is wild-type NiV-G or is a NiV-G protein that has a cytoplasmic tail truncation comprising a deletion in its cytoplasmic tail relative to wild type NiV-G sequence,   and wherein the NiV envelope pseudotyped lentivirus particle has increased viral transduction titer compared to a lentivirus particle pseudotyped with wild-type NiV-F and wild-type NiV-G.   
     
     
         16 . The method of  claim 12 , wherein the NiV-G protein comprises a deletion of at least 10 contiguous amino acid residues from the cytoplasmic tail. 
     
     
         17 . The method of  claim 12 , wherein the NiV-G protein comprises a deletion of at least 15 contiguous amino acid residues from the cytoplasmic tail. 
     
     
         18 . The method of  claim 12 , wherein the NiV-G protein comprises a deletion of at least 20 contiguous amino acid residues from the cytoplasmic tail. 
     
     
         19 . The method of  claim 12 , wherein the NiV-G protein comprises a deletion of at least 30 contiguous amino acid residues from the cytoplasmic tail. 
     
     
         20 . The method of  claim 12 , wherein the NiV-F protein or the NiV-G protein further comprises a hyperfusogenic mutation. 
     
     
         21 . The method of  claim 12 , wherein the NiV-G protein further comprises a mutation that abrogates ephrinB2 and B3 binding. 
     
     
         22 . The method of  claim 12 , wherein the nucleic acid for delivery encodes a payload chosen from: a gene therapy payload, a payload that is toxic to the cell, or an ephrin antagonist. 
     
     
         23 . The method of  claim 12 , wherein the NiV-G comprises a single chain variable fragment (scFV) directed against a cell surface molecule other than ephrinB2 and/or B3. 
     
     
         24 . The method of  claim 12 , wherein the viral transduction titer is increased greater than 2-fold. 
     
     
         25 . The method of  claim 15 , wherein the administration of the NiV envelope pseudotyped lentivirus particle comprising the nucleic acid effective for treating cancer. 
     
     
         26 . The method of  claim 15 , wherein the NiV envelope pseudotyped lentivirus particle is administered intravenously. 
     
     
         27 . A pharmaceutical composition comprising a Nipah virus (NiV) envelope pseudotyped lentivirus particle, wherein the NiV pseudotyped lentivirus particle comprises Nipah Virus fusion (NiV-F) and Nipah Virus attachment (NiV-G) proteins,
 wherein the NiV-F protein comprises a deletion in its cytoplasmic tail relative to a wild type NiV-F sequence, wherein the NiV-F protein comprises a cytoplasmic tail lacking amino residues 525-546 of SEQ ID NO: 1,   wherein the NiV-G protein is wild-type NiV-G or is a NiV-G protein that has a cytoplasmic tail truncation comprising a deletion in its cytoplasmic tail relative to wild type NiV-G sequence,   and wherein the NiV envelope pseudotyped lentivirus particle has increased viral transduction titer compared to a lentivirus particle pseudotyped with wild-type NiV-F and wild-type NiV-G.   
     
     
         28 . The composition of  claim 27 , wherein the NiV-G protein comprises a deletion of at least 10 contiguous amino acid residues from the cytoplasmic tail. 
     
     
         29 . The composition of  claim 27 , wherein the NiV-G protein comprises a deletion of at least 15 contiguous amino acid residues from the cytoplasmic tail. 
     
     
         30 . The composition of  claim 27 , wherein the NiV-G protein comprises a deletion of at least 20 contiguous amino acid residues from the cytoplasmic tail. 
     
     
         31 . The composition of  claim 27 , wherein the NiV-G protein comprises a deletion of at least 30 contiguous amino acid residues from the cytoplasmic tail. 
     
     
         32 . The composition of  claim 27 , wherein the NiV-F protein or the NiV-G protein further comprises a hyperfusogenic mutation. 
     
     
         33 . The composition of  claim 27 , wherein the NiV-G protein further comprises a mutation that abrogates ephrinB2 and B3 binding. 
     
     
         34 . The composition of  claim 27 , wherein the NiV-G comprises a single chain variable fragment (scFV) directed against a cell surface molecule other than ephrinB2 and/or B3. 
     
     
         35 . The composition of  claim 27 , wherein the viral transduction titer is increased greater than 2-fold. 
     
     
         36 . A method of administering the pharmaceutical composition of  claim 27 , the method comprising systemically administering a therapeutically effective amount of the NiV pseudotyped lentivirus particle to a subject in need thereof. 
     
     
         37 . A method of producing a Nipah virus (NiV) envelope pseudotyped lentivirus particle, the method comprising culturing producer cells comprising one or more nucleic acids for the production of the lentiviral particle under conditions for producing the lentiviral particle by the host cells,
 wherein the NiV pseudotyped lentivirus particle comprises Nipah Virus fusion (NiV-F) and Nipah Virus attachment (NiV-G) proteins,   wherein the NiV-F protein comprises a deletion in its cytoplasmic tail relative to a wild type NiV-F sequence, wherein the NiV-F protein comprises a cytoplasmic tail lacking amino residues 525-546 of SEQ ID NO: 1,   wherein the NiV-G protein is wild-type NiV-G or is a NiV-G protein that has a cytoplasmic tail truncation comprising a deletion in its cytoplasmic tail relative to wild type NiV-G sequence,   and wherein the NiV envelope pseudotyped lentivirus particle has increased viral transduction titer compared to a lentivirus particle pseudotyped with wild-type NiV-F and wild-type NiV-G.   
     
     
         38 . The method of  claim 37 , wherein the pseudotyped lentivirus particle further comprises a nucleic acid for delivery that encodes a payload chosen from: a gene therapy payload, a payload that is toxic to the cell, or an ephrin antagonist. 
     
     
         39 . The method of  claim 37 , wherein the NiV-G protein comprises a deletion of at least 10 contiguous amino acid residues from the cytoplasmic tail. 
     
     
         40 . The method of  claim 37 , wherein the NiV-G protein comprises a deletion of at least 15 contiguous amino acid residues from the cytoplasmic tail. 
     
     
         41 . The method of  claim 37 , wherein the NiV-G protein comprises a deletion of at least 20 contiguous amino acid residues from the cytoplasmic tail. 
     
     
         42 . The method of  claim 37 , wherein the NiV-G protein comprises a deletion of at least 30 contiguous amino acid residues from the cytoplasmic tail. 
     
     
         43 . The method of  claim 37 , wherein the NiV-F protein or the NiV-G protein further comprises a hyperfusogenic mutation. 
     
     
         44 . The method of  claim 37 , wherein the NiV-G protein further comprises a mutation that abrogates ephrinB2 and B3 binding. 
     
     
         45 . The method of  claim 37 , wherein the NiV-G comprises a single chain variable fragment (scFV) directed against a cell surface molecule other than ephrinB2 and/or B3. 
     
     
         46 . The method of  claim 37 , wherein the viral transduction titer is increased greater than 2-fold.

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