摘要:
A method for engineering and utilizing large DNA vectors to target, via homologous recombination, and modify, in any desirable fashion, endogenous genes and chromosomal loci in eukaryotic cells. These large DNA targeting vectors for eukaryotic cells, termed LTVECs, are derived from fragments of cloned genomic DNA larger than those typically used by other approaches intended to perform homologous targeting in eukaryotic cells. Also provided is a rapid and convenient method of detecting eukaryotic cells in which the LTVEC has correctly targeted and modified the desired endogenous gene(s) or chromosomal locus (loci) as well as the use of these cells to generate organisms bearing the genetic modification.
摘要:
Methods for identifying a compound capable of modulating activity of a target active domain, by generating a first fusion protein having an anchor component and a variable component, generating a second fusion protein having a docking domain and an active domain, wherein the anchor component and the docking domain are binding partners, then contacting the fusion proteins under conditions in which the anchor component and the docking domain bind, and determining the activity of the target domain.
摘要:
The present invention provides for a gene, designated as musk , that encodes a novel tyrosine kinase receptor expressed in high levels in denervated muscle. The invention also provides for an isolated polypeptide which activates MuSK receptor. The invention further provides for a polypeptide which is functionally equivalent to the MuSK activating polypeptide. The invention also provides assay systems that may be used to detect and/or measure ligands that bind the musk gene product. The present invention also provides for diagnostic and therapeutic methods based on molecules that activate MuSK.
摘要:
The present invention provides a method for inhibiting atrophy or causing hypertrophy in muscle cells. It further provides a method for inhibiting skeletal muscle atrophy or causing skeletal muscle hypertrophy in vertebrate animals. It also provides a method of identifying agents that may be method for inhibiting atrophy or causing hypertrophy in muscle cells.
摘要:
The present invention provides for a modified TIE-2 ligand which has been altered by addition, deletion or substitution of one or more amino acids, or by way of tagging, with for example, the Fc portion of human IgG-1, but which retains its ability to bind the TIE-2 receptor. The invention further provides for a modified TIE-2 ligand which is a chimeric TIE-2 ligand comprising at least a portion of a first TIE-2 ligand and a portion of a second TIE-2 ligand which is different from the first. In a specific embodiment, the invention further provides for a chimeric TIE ligand comprising at least a portion of TIE-2 Ligand-1 and a portion of TIE-2 Ligand-2. In addition the present invention provides for isolated nucleic acid molecule encoding the modified TIE-2 ligands described. The invention also provides for therapeutic compositions as well as a method of blocking blood vessel growth, a method of promoting neovascularization, a method of promoting the growth or differentiation of a cell expressing the TIE receptor, a method of blocking the growth or differentiation of a cell expressing the TIE receptor and a method of attenuating or preventing tumor growth in a human.
摘要:
Modified chimeric polypeptides with improved pharmacokinetics are disclosed. Specifically, modified chimeric Flt1 receptor polypeptides that have been modified in such a way as to improve their pharmacokinetic profile are disclosed. Also disclosed are methods of making and using the modified polypeptides including but not limited to using the modified polypeptides to decrease or inhibit plasma leakage and/or vascular permeability in a mammal. Also disclosed are methods of treating diseases in which plasma leakage and/or vascular permeability occurs, for example, inflammatory skin diseases.
摘要:
The present invention provides for an isolated nucleic acid molecule encoding a member of the TIE ligand family. The present invention also provides for an isolated nucleic acid molecule encoding TIE ligand-3 or TIE ligand-4. In addition, the invention provides for a receptor body which specifically binds TIE ligand-3 or TIE ligand-4. The invention also provides an antibody which specifically binds TIE ligand-3 or TIE ligand-4. The invention further provides for an antagonist of TIE. The invention also provides for therapeutic compositions as well as a method of blocking blood vessel growth, a method of promoting neovascularization, a method of promoting the growth or differentiation of a cell expressing the TIE receptor, a method of blocking the growth or differentiation of a cell expressing the TIE receptor and a method of attenuating or preventing tumor growth in a human.
摘要:
L'invention concerne des systèmes d'analyses qui peuvent être utilisés pour détecter et/ou mesurer l'activité de la neurotrophine et pour identifier des agents ayant une activité semblable à celle de la neurotrophine. L'invention se base, au moins en partie, sur la découverte que le proto-oncogène trkB code un récepteur de la tyrosine kinase qui peut servir de protéine de liaison fonctionnelle pour BDNF et NT-3. L'invention concerne également des procédés diagnostiques et thérapeutiques fondés sur l'interaction entre BDNF et/ou NT-3 et trkB, et pour plusieurs molécules réceptrices d'orphan.
摘要:
Compositions and methods are provided for making one or more targeted genetic modifications at a target genomic locus by employing homologous recombination facilitated by single or double-strand break at or near the target genomic locus. Compositions and methods for promoting efficiency of homologous recombination between an LTVEC and a target genomic locus in prokaryotic or eukaryotic cells using engineered nucleases are also provided.