Nuclear localization signal of lentiviral integrase and methods of use thereof
AssigneeThe Rockefeller University
InventorsMark Muesing, Tshaka Cunningham
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Abstract
The present invention provides novel peptides, nucleic acids, vectors, compounds, compositions and methods for regulating nuclear import The present invention also relates to a lentiviral NLS, and methods of use thereof for inhibiting HIV pathogenesis and disease progression, and for gene delivery methods
Claims95
A lentiviral nuclear localization signal, comprising an amino acid sequence corresponding to the formula:
- R5(R6)2FRVYR1R3R2R8R3NPLWR3GPR8KR4R5WR3GEGA(R4)3R6DR6SR6R4KVR4PR(R3)2R8KIR4R3D, wherein:
- R1=an aromatic amino acid
- R2=an acidic amino acid
- R3=a basic amino acid
- R4=a branched chain amino acid
- R5=a hydrophobic amino acid
- R6=a polar amino acid
- R7=a proline or serine amino acid residue
- R8 =a small amino acid residue
- lower case letters=the preferred amino acid residue, however substitutions with amino acid residues from disparate groups are possible as well.
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The vector of claim 98, further comprising a second nucleic acid.
23-26. (canceled)
29-49. (canceled)
The mutated lentiviral nuclear localization signal of 52, comprising an amino acid sequence at least 75% homologous to SEQ ID NO:
- 67-129, 139, 140, 141, 142, 143, 144, 145, 146 or 147.
56-72. (canceled)
74-87. (canceled)
An isolated polynucleotide, comprising a nucleic acid encoding for a lentiviral nuclear localization signal, wherein said lentiviral nuclear localization signal, comprises an amino acid sequence corresponding to the formula:
- R5(R6)2FRVYR1R3R2R8R3NPLWR3GPR8KR4R5WR3GEGA(R4)3R6DR6SR6R4 KVR4PR(R3)2R8KIR4R3D, wherein:
- R1=an aromatic amino acid
- R2=an acidic amino acid
- R3=a basic amino acid
- R4=a branched chain amino acid
- R5=a hydrophobic amino acid
- R6=a polar amino acid
- R7=a proline or serine amino acid residue
- R8=a small amino acid residue
- lower case letters=the preferred amino acid residue, however substutions with amino acid residues from disparate groups are possible as well.
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A method of targeting an agent to the nucleus of a cell, comprising the steps of:
- contacting a cell with a lentiviral nuclear localization signal, wherein said lentiviral nuclear localization signal is covalently attached to said agent;
- and
- culturing said cell under conditions facilitating nuclear import, thereby targeting an agent to the nucleus of a cell.
106-107. (canceled)
111-117. (canceled)
A method of targeting a protein of interest to the nucleus of a cell, comprising the steps of:
- contacting a cell with a vector, comprising a nucleic acid encoding a lentiviral nuclear localization signal, wherein said nucleic acid encoding a lentiviral nuclear localization signal is fused in frame to a nucleic acid encoding a protein of interest;
- thereby targeting a protein of interest to the nucleus of a cell.
128-134. (canceled)
143-164. (canceled)
181-186. (canceled)
Dependencies are inferred from the claim text.