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

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: 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: 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: Disclosed herein are 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 preparing 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.

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: 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 present invention relates to methods for the detection of substances capable of modulating or inhibiting pathological tau-tau protein association. The methods of the present invention are particularly useful in screening substances for the prophylaxis and treatment of Alzheiemer's disease.

Abstract: The present invention relates generally to methods and compositions for the diagnosis, modeling and treatment of tau-related pathologies. In particular, the present invention shows that mutations in the tau gene lead to neurofibrillary tangle formation. More specifically gene mutations are described that lead to alterations in ratios of tau isoforms are shown to lead to the formation of abnormal tau filaments.

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.