Peptides and uses

摘要

Disclosed herein are zinc finger peptides having at least 4 zinc finger domains, such as 6, 11, 12 or 18 zinc finger domains. The zinc finger peptides may be fused to effector domains for modulating gene expression. Zinc finger peptides of the invention are useful for targeting trinucleotide-repeat sequences in mutant genes and may have applications in gene therapy. The zinc finger peptides may have nucleic acid recognition sequences according to SEQ ID NO: 101. Also disclosed are methods for constructing poly-zinc finger peptides having arrays of at least 8 zinc finger domains, along with zinc finger frameworks that may be useful for selecting zinc finger peptides from libraries.

主权项

1. A zinc finger peptide comprising the sequence:N′-[(Formula 2)-X6]n0-{[(Formula 2)-X5-(Formula 2)-X6]n1-[(Formula 2)-X5-(Formula 2)-XL]}n2-[(Formula 2)-X5-(Formula 2)-X6]n3-[(Formula 2)-X5-(Formula 2)]-[X6-(Formula 2)-]n4-C′,
wherein n0 is 0 or 1, n1 is from 1 to 4, n2 is 1 or 2, n3 is from 1 to 4, n4 is 0 or 1, X5 is a linker sequence of 5 amino acids, X6 is a linker sequence of 6 or 7 amino acids, and XL is a linker sequence of at least 8 amino acids, and Formula 2 is a zinc finger domain of the sequence -X0-2 CX1-5 CX2-7 X−1 x+1 x+2 x+3 x+4 x+5 x+6 HX3-6 H/C-, wherein X is any amino acid, the numbers in subscript indicate the possible numbers of residues represented by X at that position, and the number in superscript indicates the position of the amino acid in the recognition sequence of the zinc finger domain; wherein the zinc finger peptide comprises from 8 to 32 zinc finger domains,
comprises at least the sequence of SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 10, SEQ ID NO: 12, SEQ ID NO: 14 or SEQ ID NO: 108 or a sequence having at least 90% sequence identity thereto, andat least one zinc finger domain comprises a X−1 X+1 X+2 X+3 X+4 X+5 X+6 recognition sequence according to SEQ ID NO: 101.