Nucleic acid binding polypeptides
AssigneeGendaq Limited
InventorsMichael Moore, Mark Isalan, Lindsey Reynolds, Christopher Ullman, John Girdlestone, Christophe Demaison, Yen Choo
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Abstract
We disclose a polypeptide capable of binding to a nucleic acid comprising a receptor nucleotide sequence.
Claims41
A polypeptide capable of binding to a nucleic acid comprising a receptor nucleotide sequence.
A polypeptide according to any preceding claim, in which the receptor is capable of functioning as a receptor for viral infection.
A polypeptide according to any preceding claim, in which the receptor is capable of functioning as a receptor for infection by Human Immunodeficiency Virus (HIV).
A polypeptide according to any preceding claim, in which the receptor is selected from the group consisting of:
- CD4, CXCR-4, CCR5, CCR3 and CCR2b.
A polypeptide according to any preceding claim, in which the polypeptide comprises a zinc finger motif having a general primary structure:
- 16 (A′) X0-2 C X1-5 C X2-7 X X X X X X X H X3-6 H/C −1 1 2 3 4 5 6 7
- where X is any amino acid, and the numbers in subscript indicate the possible numbers of residues represented by X, in which the receptor comprises a CXCR4 receptor, and in which the polypeptide comprises three zinc fingers F1, F2 and F3, at least one of the amino acids at positions −1, 3, and 6 of F1, −1, 3 and 6 of F2 and −1, 3 and 6 of F3 being selected from amino acids specified in the following table:
- 17 F1:
- amino acid −1 D, R, K, R 3 T, E, D 6 E, R F2 −1 R, Q, T 3 D, T, H, N 6 R, K, R, A F3 −1 R, Q, D 3 D 6 R, Q, K
A polypeptide according to any preceding claim, in which the polypeptide comprises one or more amino acid sequences selected from the group consisting of consensus sequences 1 to 36 shown in Table 1, a variant of one or more thereof, and polypeptides comprising combinations of two or more thereof.
A polypeptide according to any preceding claim, in which the polypeptide comprises a zinc finger comprising six zinc finger motifs selected from the group consisting of:
- CXCR4-5-1, CXCR4-10-1, CXCR4-10-3, TNFR1-4-2, TNFR1-7-9, TNFR1-9-12, and TNFR1-7-10.
A polypeptide according to any preceding claim, which further comprises a transcriptional effector domain.
A polypeptide according to any preceding claim selected by phage display.
A polypeptide according to any preceding claim which is engineered on the basis of rational design.
A composition comprising a pharmaceutically effective amount of a polypeptide according to any preceding claim, together with a pharmaceutically acceptable excipient, diluent or carrier.
Use of a zinc finger polypeptide, or a nucleic acid encoding such a polypeptide, to modulate transcription of a receptor nucleotide sequence.
A method of treating or preventing a disease in a patient caused by a virus, the method comprising administering a nucleic acid binding polypeptide capable of binding to a nucleic acid sequence comprising a receptor nucleotide sequence, in which the receptor is capable of functioning as a receptor for infection by the virus, or a nucleic acid encoding such a polypeptide, to the patient.
A polypeptide capable of binding to a nucleic acid sequence comprising a receptor nucleotide sequence, in which the receptor is capable of functioning as a receptor for infection by the virus, or a nucleic acid encoding such a polypeptide, for use in a method of treatment or prevention of a disease caused by a virus.
Use of a nucleic acid polypeptide capable of binding to a nucleic acid sequence comprising a receptor nucleotide sequence, in which the receptor is capable of functioning as a receptor for infection by the virus, or a nucleic acid encoding such a polypeptide, in the preparation of a medicament for use in the treatment or prevention of a disease caused by a virus in a patient.
A method of treating or preventing a disease in a patient associated with an immune response, the method comprising administering a nucleic acid binding polypeptide capable of binding to a nucleic acid sequence comprising a receptor nucleotide sequence, in which the receptor is involved in the immune response, or a nucleic acid encoding such a polypeptide, to the patient.
A polypeptide capable of binding to a nucleic acid sequence comprising a receptor nucleotide sequence, in which the receptor is involved in an immune response, or a nucleic acid encoding such a polypeptide, for use in a method of treatment or prevention of a disease associated with an immune response.
Use of a nucleic acid polypeptide capable of binding to a nucleic acid sequence comprising a receptor nucleotide sequence, in which the receptor is involved in an immune response, or a nucleic acid encoding such a polypeptide, in the preparation of a medicament for use in the treatment or prevention of a disease associated with an immune response.
A method of downregulating the expression of a receptor involved in viral infection or an immune response, the method comprising:
- (a) providing a nucleic acid binding polypeptide capable of binding to a nucleic acid sequence comprising a nucleotide sequence of the receptor;
- (b) providing a native nucleic acid sequence comprising one or more nucleotide sequences capable of being bound by the nucleic acid binding polypeptide;
- and (b) contacting the nucleic acid binding polypeptide with the native nucleic acid sequence.
A method of reducing viral titre in a system comprising a host cell and a virus, the method comprising administering to the system or any of its components a polypeptide capable of binding to a nucleotide sequence of a receptor involved in viral infection, or a nucleic acid encoding such a polypeptide.
A method of downregulating a viral function in a cell, the method comprising contacting the cell with a polypeptide capable of binding to a nucleotide sequence of a receptor involved in viral infection, or a nucleic acid encoding such a polypeptide.
Dependencies are inferred from the claim text.