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US 12,061,187 B2Granted
Ligand discovery and gene delivery via retroviral surface display
AssigneeMassachusetts Institute of Technology
InventorsMichael Birnbaum, Connor Dobson
Life of this patent
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Abstract
Compositions of retroviruses and methods of using the same for gene delivery, wherein the retroviruses comprise a viral envelope protein comprising at least one mutation that diminishes its native function, a non-viral membrane-bound protein comprising a membrane-bound domain and an extracellular targeting domain.
Claims20
A method of delivering a nucleic acid to a cell, the method comprising:
- (i) providing a retrovirus comprising (a) the nucleic acid and (b) a viral envelope that comprises at least two different proteins:
- 1) a viral envelope protein comprising at least one mutation that diminishes the native viral tropism of the mutated viral envelope protein compared to the non-mutated viral envelope protein, wherein the viral envelope protein is a vesicular stomatitis virus (VSV)-G envelope protein that comprises an amino acid substitution at position K47 and/or an amino acid substitution at position R354, said positions with reference to SEQ ID NO:
- 13 or a cocal virus G envelope protein that comprises an amino acid substitution at position K64 and/or an amino acid substitution at position R371, said positions with reference to SEQ ID NO:
- 51;
- and
- 2) a non-viral membrane-bound protein comprising a transmembrane domain and an extracellular targeting domain that is capable of binding to a ligand expressed on the surface of the cell;
- and
- (ii) contacting the retrovirus with the cell,
- thereby delivering the nucleic acid to the cell.
6 more elements
The method of 7, wherein the non-viral membrane-bound protein further comprises a peptide displayed by the class I MHC protein or the class II MHC protein.
Dependencies are inferred from the claim text.