Ligand discovery and gene delivery via retroviral surface display
AssigneeMassachusetts Institute of Technology
InventorsMichael Birnbaum, Connor Dobson
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Abstract
Compositions of retroviruses and methods of using the same for gene delivery are disclosed, 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.
Claims30
A composition comprising a lentivirus, the lentivirus comprising:
- (a) a nucleic acid;
- (b) a viral envelope comprising
- (i) a vesicular stomatitis virus (VSV)-G envelope protein comprising an amino acid sequence at least 95% identical to SEQ ID NO:
- 13, wherein the VSV-G envelope protein comprises one or more amino acid mutations at position 47 (lysine, K) and/or position 354 (arginine, R), wherein the amino acid mutation(s) diminish the native viral tropism of the VSV-G envelope protein compared to the non-mutated VSV-G envelope protein;
- and
- (ii) a non-viral membrane-bound protein comprising a transmembrane-domain and an extracellular targeting domain that binds to a ligand expressed on the surface of a T cell or a B cell.
A method of delivering a nucleic acid to a T cell or B cell, the method comprising:
- (a) providing a composition comprising a lentivirus, the lentivirus comprising:
- a nucleic acid and a viral envelope comprising (i) a VSV-G envelope protein comprising an amino acid sequence at least 95% identical to SEQ ID NO:
- 13, wherein the VSV-G envelope protein comprises one or more amino acid mutations at position 47 (lysine, K) and/or position 354 (arginine, R), wherein the amino acid mutation(s) diminish the native viral tropism of the VSV-G envelope protein compared to the non-mutated VSV-G envelope protein;
- and (ii) a non-viral membrane-bound protein comprising a transmembrane-domain and an extracellular targeting domain that binds to a ligand expressed on the surface of a T cell or a B cell;
- (b) contacting the composition with the T cell or B cell,
- thereby delivering the nucleic acid to the T cell or B cell.
A composition comprising a lentivirus, the lentivirus comprising
- (a) a nucleic acid;
- (b) a viral envelope comprising:
- (i) a VSV-G envelope protein comprising an amino acid sequence at least 95% identical to SEQ ID NO:
- 13, wherein the VSV-G envelope protein comprises one or more amino acid mutations at position 47 (lysine, K) and/or position 354 (arginine, R), wherein the amino acid mutation(s) diminish the native viral tropism of the VSV-G envelope protein compared to the non-mutated VSV-G envelope protein;
- and
- (ii) a non-viral membrane-bound protein comprising a transmembrane domain and an extracellular targeting domain that comprises an anti-CD3 antibody.
A method of delivering a nucleic acid to a T cell, the method comprising:
- (a) providing a composition comprising a lentivirus, the lentivirus comprising:
- a nucleic acid and a viral envelope comprising (i) a VSV-G envelope protein comprising an amino acid sequence at least 95% identical to SEQ ID NO:
- 13, wherein the VSV-G envelope protein comprises one or more amino acid mutations at position 47 (lysine, K) and/or position 354 (arginine, R), wherein the amino acid mutation(s) diminish the native viral tropism of the VSV-G envelope protein compared to the non-mutated VSV-G envelope protein;
- and (ii) a non-viral membrane-bound protein comprising a transmembrane domain and an extracellular targeting domain that comprises an anti-CD3 antibody;
- (b) contacting the lentivirus with the T cell,
- thereby delivering the nucleic acid to the T cell.
Dependencies are inferred from the claim text.