Back to results
US 12,631,621 B2Granted
Ligand discovery and gene delivery via retroviral surface display
AssigneeMassachusetts Institute of Technology
InventorsMichael Birnbaum, Connor Dobson
Life of this patent
Estimating the term…
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 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 cell.
3 more elements
A method of delivering a nucleic acid to a cell, the method comprising:
- (a) providing a 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 cell;
- (b) contacting the lentivirus with the cell,
- thereby delivering the nucleic acid to the cell.
3 more elements
A lentivirus, comprising
- (a) a nucleic acid encodes an mRNA, a double-stranded DNA, an antisense RNA, a microRNA, a gene of interest, or a protein;
- (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.
3 more elements
A method of delivering a nucleic acid to a T cell, the method comprising:
- (a) providing a lentivirus comprising:
- (i) a nucleic acid encoding an mRNA, a double-stranded DNA, an antisense RNA, a microRNA, a gene of interest, or a protein;
- and a viral envelope comprising
- (ii) 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
- (iii) 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.
6 more elements
Dependencies are inferred from the claim text.