Modified paramyxoviridae attachment glycoproteins
AssigneeSana Biotechnology, Inc.
InventorsChristopher BANDORO, Lauren Pepper MACKENZIE, Jagesh Vijaykumar SHAH, Kyle Marvin TRUDEAU
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Abstract
Provided herein are lipid particles, such as lenti viral particles, that incorporate or are pseudotyped with a variant Nipah Virus G (NiV-G) envelope glycoprotein, and in some aspects also a fusion (F) protein such as a NiV-F protein or a biologically active portion or variant thereof. Also provided are polynucleotides encoding the variant NiV-G and producer cells for preparation of the lipid particles, such as lentiviral particles, containing the variant NiV-G proteins, as well as methods for preparing and using the lipid particles, such as lentiviral particles.
Claims218
A lipid particle, comprising:
- (a) a lipid bilayer;
- (b) a paramyxovirus fusion (F) protein or biologically active portion thereof;
- and
- (c) a variant Nipah virus G glycoprotein (NiV-G) comprising a modified cytoplasmic tail, wherein the modified cytoplasmic tail comprises:
- (i) a heterologous cytoplasmic tail or a truncated portion thereof from a glycoprotein from another virus or a virus-associated protein, wherein the variant NiV-G is a chimeric protein;
- (ii) a truncated NiV-G cytoplasmic tail that has a deletion of between 26 and 40 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein cytoplasmic tail set forth in SEQ ID NO:
- 4, with the proviso that the cytoplasmic tail is not deletion of residues 2-32, 2-33, 2-34, 2-35, or 2-36 of SEQ ID NO:4;
- or
- (iii) a modified NiV-G cytoplasmic that comprises the amino acid substitution I20N and/or V24I in the cytoplasmic tail set forth in SEQ ID NO:4,
- wherein the F protein or the biologically active portion thereof and the variant NiV-G are exposed on the outside of the lipid bilayer.
A pseudotyped lentiviral particle, comprising:
- (a) a paramyxovirus fusion (F) protein or biologically active portion thereof;
- and
- (b) a variant Nipah virus G glycoprotein (NiV-G) comprising a modified cytoplasmic tail, wherein the modified cytoplasmic tail comprises:
- (i) a heterologous cytoplasmic tail or a truncated portion thereof from a glycoprotein from another virus or a virus-associated protein, wherein the variant NiV-G is a chimeric protein;
- (ii) a truncated NiV-G cytoplasmic tail that has a deletion of between 26 and 40 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein cytoplasmic tail set forth in SEQ ID NO:
- 4, with the proviso that the truncated cytoplasmic tail is not deletion of residues 2-32, 2-33, 2-34, 2-35, or 2-36 of SEQ ID NO:4;
- or
- (iii) a modified NiV-G cytoplasmic that comprises the amino acid substitution I20N and/or V24I in the cytoplasmic tail set forth in SEQ ID NO:4,
- wherein the F protein or the biologically active portion thereof and the variant NiV-G are exposed on the outside of the lentiviral vector.
A polynucleotide comprising a nucleic acid molecule encoding a variant Nipah virus G glycoprotein (NiV-G) comprising a modified cytoplasmic tail, wherein the modified cytoplasmic tail comprises:
- (i) a heterologous cytoplasmic tail or a truncated portion thereof from a glycoprotein from another virus or a virus-associated protein, wherein the variant NiV-G is a chimeric protein;
- (ii) a truncated NiV-G cytoplasmic tail that has a deletion of between 26 and 40 contiguous amino acid residues at or near the N-terminus of the wild-type NiV-G protein cytoplasmic tail set forth in SEQ ID NO:
- 4, with the proviso that the cytoplasmic tail is not deletion of residues 2-32, 2-33, 2-34, 2-35, or 2-36 of SEQ ID NO:4;
- and
- (iii) a modified NiV-G cytoplasmic that comprises the amino acid substitution I20N and/or V24I in the cytoplasmic tail set forth in SEQ ID NO:4.
Dependencies are inferred from the claim text.