Abstract: Methods for delivering non-mitochondrial proteins to mitochondria are provided. Also provided are nucleic acid constructs comprising a coding sequence encoding a DNA-binding polypeptide, fused to a mitochondrial targeting sequence (MTS) and a nuclear export signal (NES), and the encoded proteins. The construct successfully delivers DNA binding proteins to the mitochondrion. A chimeric methylase based on the above construct is successfully delivered to mitochondria, resulting in modification of mtDNA.

Abstract: Methods for delivering non-mitochondrial proteins to mitochondria are provided. Also provided are nucleic acid constructs comprising a coding sequence encoding a DNA-binding polypeptide, fused to a mitochondrial targeting sequence (MTS) and a nuclear export signal (NES), and the encoded proteins. The construct successfully delivers DNA binding proteins to the mitochondrion. A chimeric methylase based on the above construct is successfully delivered to mitochondria, resulting in modification of mtDNA.

Abstract: Methods for delivering non-mitochondrial proteins to mitochondria are provided. Also provided are nucleic acid constructs comprising a coding sequence encoding a DNA-binding polypeptide, fused to a mitochondrial targeting sequence (MTS) and a nuclear export signal (NES), and the encoded proteins. The construct successfully delivers DNA binding proteins to the mitochondrion. A chimeric methylase based on the above construct is successfully delivered to mitochondria, resulting in modification of mtDNA.

Abstract: The invention provides a method for designing a nucleic acid binding protein of the Cys2-His2 zinc finger class capable of binding to a nucleic acid quadruplet in a target nucleic acid sequence, wherein binding to base 4 of the quadruplet by an alpha-helical zinc finger nucleic acid binding motif in the protein is determined as follows: if base 4 in the quadruplet is A, then position +6 in the alpha-helix is Glu, Asn or Val; if base 4 in the quadruplet is C, then position +6 in the alpha-helix is Ser, Thr, Val, Ala, Glu or Asn; if base 4 of the quadruplet is G, the position +6 in the alpha helix is Arg or Lys; if position 4 in the quadruplet is T, then position +6 in the alpha helix is Ser, Thr, Val or Lys.

Abstract: The invention relates to a zinc finger polypeptide library in which each polypeptide comprises more than one zinc finger which has been at least partially randomized, and to a set of zinc finger polypeptide libraries which encode overlapping zinc finger polypeptides, each polypeptide comprising more than one zinc finger which has been at least partially randomized, and which polypeptide may be assembled after selection to form a multifinger zinc finger polypeptide.

Abstract: A composition and use thereof for the prophylaxis or treatment of Alzheimer's disease, motor neurone disease, Lewy body disease, Pick's disease or progressive supranuclear palsy. The composition includes an agent which modulates or inhibits tau-tau association and which does not inhibit tau-tubulin binding. In the method the agent is administered to an individual in order to achieve the desired therapeutic effect. Preferably the agent which is administered is a phenothiazine compound.

Abstract: We describe a method of producing a modified nucleic acid binding polypeptide, the method comprising the steps of: (a) providing a nucleic acid binding polypeptide comprising a plurality of nucleic acid binding modules; (b) selecting a first binding domain consisting of one or two contiguous nucleic acid binding modules; (c) selecting a second binding domain consisting of one or two contiguous nucleic acid binding modules; and (d) introducing a flexible linker sequence to link the first and second binding domains, the flexible linker sequence comprising five or more amino acid residues. Use of structured linkers, alone or in combination with flexible linkers, is also disclosed.

Abstract: The application provides methods of designing zinc finger binding polypeptides for binding to particular target sequences comprising overlapping nucleotide quadruplets.

Abstract: The invention relates to a zinc finger polypeptide library in which each polypeptide comprises more than one zinc finger which has been at least partially randomized, and to a set of zinc finger polypeptide libraries which encode overlapping zinc finger polypeptides, each polypeptide comprising more than one zinc finger which has been at least partially randomized, and which polypeptide may be assembled after selection to form a multifinger zinc finger polypeptide.

Abstract: Methods for delivering non-mitochondrial proteins to mitochondria are provided. Also provided are nucleic acid constructs comprising a coding sequence encoding a DNA-binding polypeptide, fused to a mitochondrial targeting sequence (MTS) and a nuclear export signal (NES), and the encoded proteins. The construct successfully delivers DNA binding proteins to the mitochondrion. A chimeric methylase based on the above construct is successfully delivered to mitochondria, resulting in modification of mtDNA.

Abstract: Disclosed herein are methods and compositions for modulation of gene expression, with single-gene specificity, in a human-sized genome.

Abstract: A composition and use thereof for the prophylaxis or treatment of Alzheimer's disease, motor neurone disease, Lewy body disease, Pick's disease or progressive supranuclear palsy. The composition includes an agent which modulates or inhibits tau-tau association and which does not inhibit tau-tubulin binding. In the method the agent is administered to an individual in order to achieve the desired therapeutic effect. Preferably the agent which is administered is a phenothiazine compound.

Abstract: The application provides methods of designing zinc finger binding polypeptides for binding to particular target sequences comprising overlapping nucleotide quadruplets.

Abstract: Disclosed herein are methods for designing DNA binding proteins comprising a plurality of zinc fingers and methods for binding the proteins to target nucleotide sequences in cells.

Abstract: Disclosed herein are methods for designing DNA binding proteins comprising a plurality of zinc fingers and methods for binding the proteins to target nucleotide sequences in cells.

Abstract: The invention provides a method for designing a nucleic acid binding protein of the Cys2-His2 zinc finger class capable of binding to a nucleic acid quadruplet in a target nucleic acid sequence, wherein binding to base 4 of the quadruplet by an alpha-helical zinc finger nucleic acid binding motif in the protein is determined as follows: if base 4 in the quadruplet is A, then position +6 in the alpha-helix is Glu, Asn or Val; if base 4 in the quadruplet is C, then position +6 in the alpha-helix is Ser, Thr, Val, Ala, Glu or Asn; if base 4 of the quadruplet is G, the position +6 in the alpha helix is Arg or Lys; if position 4 in the quadruplet is T, then position +6 in the alpha helix is Ser, Thr, Val or Lys.

Abstract: Disclosed are libraries of DNA sequences encoding zinc finger binding motifs for display on a particle, together with methods of designing zinc finger binding polypeptides for binding to a particular target sequence and, inter alia, use of designed zinc finger polypeptides for various in vitro or in vivo applications.

Abstract: Disclosed are libraries of DNA sequences encoding zinc finger binding motifs for display on a particle, together with methods of designing zinc finger binding polypeptides for binding to a particular target sequence and, inter alia, use of designed zinc finger polypeptides for various in vitro or in vivo applications.

Abstract: Disclosed are libraries of DNA sequences encoding zinc finger binding motifs for display on a particle, together with methods of designing zinc finger binding polypeptides for binding to a particular target sequence and, inter alia, use of designed zinc finger polypeptides for various in vitro or in vivo applications.

Abstract: Disclosed are libraries of DNA sequences encoding zinc finger binding motifs for display on a particle, together with methods of designing zinc finger binding polypeptides for binding to a particular target sequence and, inter alia, use of designed zinc finger polypeptides for various in vitro or in vivo applications.