Abstract: Disclosed herein are a cell chip and a method for manufacturing the same. The cell chip may include: a substrate; and a first contact member disposed on the substrate, wherein a top end of the first contact member is provided with a first inclined contact surface inclined with respect to the substrate.

Abstract: Focused libraries of vectors or genetic packages that display, display and express, or comprise a member of a diverse family of antibody peptides, polypeptides or proteins and collectively display, display and express, or comprise at least a portion of the focused diversity of the family. The libraries have length and sequence diversities that mimic that found in native human antibodies.

Abstract: The present invention provides a method of determining bacterial metastructure by integrating multiple genome-scale information yielded by high-throughput technologies. The metastructure constructs a universal metabolic engineering platform enabling a rational design of bacterial strains through optimization of gene and protein expression.

Abstract: A selective targeting method is disclosed comprising contacting a library of ligands, particularly a peptide library, with an anti-target to allow the ligands to bind to the anti-target; separating the non-binding ligands from the anti-target bound ligands, contacting the non-binding anti-target ligands with a target allowing the unbound ligands to bind with the target to form a target-bound ligand complex; separating the target-bound ligand complex from ligands which do not bind to the target, and identifying the target-bound ligands on the target-bound ligand complex wherein the target-bound ligands have a KD in the range of about 10?7 to 10?10 M. Additionally claimed are the ligands identified according to the method.

Abstract: The invention relates to Anti-TEM 1 anti-bodies or antigen-binding fragments thereof, yeast libraries comprising the same, and prophylactic, diagnostic, and therapeutic methods using the same.

Abstract: The present invention relates to a system and method for controlling peptide display valency on virus-like particles (VLPs), especially including MS2 VLPs. In this method, large amounts of wild-type and low quantities of single-chain dimer coat proteins may be produced from a single RNA. Valency is controlled in immunogen (vaccine) production by providing a system that allows the production of large amounts of wild-type and low quantities of single-chain dimer coating proteins from a single RNA, allowing facile adjustment of display valency levels on VLPs, especially MS2 VLPS over a wide range, from few than one-on average—to as many as ninety per particle. This facilitates the production of immunogens and vaccines, including VLPs exhibiting low valency.

Abstract: A biochip includes a plurality of microchannels; and a plurality of probes disposed in an inner wall of each of the plurality of microchannels forming a one-dimensional array. The one-dimensional array of probes are configured to react with a sample in the microchannel. The plurality of microchannels are arranged such that the plurality of probes of the plurality of microchannels form a two-dimensional or three-dimensional array.

Abstract: Provided herein are methods of integrating one or more exogenous nucleic acids into one or more selected target sites of a host cell genome. In certain embodiments, the methods comprise contacting the host cell genome with one or more integration polynucleotides comprising an exogenous nucleic acid to be integrated into a genomic target site, and a nuclease capable of causing a double-strand break near or within the genomic target site.

Abstract: Methods of making and using bacterial display polypeptide libraries using circularly permuted OmpX (CPX) variants are disclosed. The invention further relates to methods for enhancing the display of proteins and peptides at the surface of bacteria by optimizing linkers and incorporating mutations at positions 165 and 166 of CPX.

Abstract: The present invention concerns a method of directing evolution of a target polynucleotide of interest for obtaining variants of this target polynucleotide, as well as a method to generate genetic variability by preparing a cell library. This invention also relates to a method to isolate or to screen variants of a polynucleotide or variants of a protein able to impact the phenotype of a cell or to confer a desired phenotype to target cells, and to identify theses polynucleotide variants or protein variants responsible for this phenotype.

Abstract: Described herein is a method that generally includes infecting a host cell with a rescue adenovirus, wherein the rescue adenovirus genome comprises a loxP site and encodes at least one marker, and wherein the host cell comprises a library of polynucleotides that complement the adenovirus genome marker and encode a detectable polypeptide; incubating the infected host cell under conditions effective to permit recombination between the adenovirus genome and one or more of the library polynucleotides and the production of recombinant adenovirus particles comprising at least on detectable polypeptide; and detecting the at least one detectable polypeptide. Also described are adenovirus libraries constructed using such a method.

Abstract: The present invention concerns donor-specific antibody libraries derived from a patient donor who has suffered from, or is suffering from one or more diseases discussed herein. The present invention also concerns the method of making and using the donor-specific antibodies. The present invention further concerns the neutralizing antibodies obtained from the donor-specific antibody libraries and the methods of using these antibodies for the prevention/treatment of human disease.

Abstract: A population of iPS cells derived from somatic cells from a spinal muscular atrophy patient is disclosed. In one embodiment of the invention, the cells have been cultured to produce neural cells. In another embodiment, the invention is a method of testing compounds for their ability to modify cellular SMN levels comprising the steps of obtaining a population of iPS cells derived from a spinal muscular atrophy patient or cells derived from the iPS cells, and examining the effect of a test compound on SMN levels.

Abstract: The invention relates to a method to generate rational libraries comprising genetic elements which are involved in transcriptional and/or translational regulation of a gene and devised to increase the production yield of the encoded protein as well as to the rational library and to the application of said rational library.

Abstract: Methods are provided for the display of a complex homodimer protein on the surface of a bacteriophage particle and combinatorial synthetic libraries of such proteins displayed as a fusion polypeptide with filamentous phage pIX coat protein. Heterodimeric or more complex interchain bonded structure, such as disulfide-linked, multimeric proteins, may be displayed using the method of the invention.

Abstract: Improved bacterial secretion signals derived from pelB and ompA are provided. The improved variants enhance bacterial membrane secretion are thus useful for production of proteins secreted from bacteria including proteins displayed on filamentous phage particles, and, in particular, proteins requiring oxidative formation of covalent bonds, such as disulfide bonds within or between polypeptide chains in order to form a correctly folded and functional protein structure. Described herein are methods for the multivalent display of complex dimeric proteins on the surface of a bacteriophage particle and combinatorial synthetic libraries of such proteins displayed as a fusion polypeptide with filamentous phage pIX coat protein. Heterodimeric or more complex interchain bonded structures may also be displayed using the method of the invention.

Abstract: Methods to improve the tropism or other features of a virus are disclosed. Such methods can be used to prepare, e.g., DNA or plasmid libraries of variants of a gene encoding a viral capsid or envelope protein having a randomly inserted restriction site, libraries of viral clones with such variant genes with a randomly inserted restriction site or polypeptide sequence targeting a receptor expressed by a specific type of mammalian cells. Described are also methods to prepare mosaic viruses, i.e., viral particles wherein copies of one or more capsid or envelope proteins originate from different sources. These methods can be used to prepare mosaic viruses of a specific mixture of wild-type and mutant proteins, or of different types of mutant proteins.

Abstract: A method for producing a bilayer, the method comprising: (a) providing a hydrated support and a hydrophilic body immersed in a hydrophobic medium; wherein a first monolayer of amphipathic molecules is formed on an interface between the hydrophobic medium and the hydrophilic body and a second monolayer of amphipathic molecules is formed on an interface between the hydrophobic medium and the hydrated support; and (b) bringing the first monolayer into contact with the second monolayer to form a bilayer of amphipathic molecules, wherein at least part of a cell membrane, comprising cell membrane constituents, is provided in or on the hydrated support and/or in the hydrophilic body, and such that constituents of the cell membrane incorporate into the bilayer during or after the bilayer formation. A bilayer produced by the method of the invention, and uses of the bilayer.

Abstract: The invention relates to a measuring device for measuring at least one property of cells or vesicles, characterized in that is divided into two chambers by a hydrophobic partition having a horizontal opening, these chambers containing electrolyte solution and said opening being closed by a lipid double layer. The invention is characterized in that at least one cell or vesicle contacts the lipid double layer. The invention also relates to methods involving the use of the measuring device and to arrays, measuring chambers and microtitration plates all suited therefor.

Abstract: The invention pertains to a natural-variant combinatorial library of fibronectin Type 3 domain (Fn3) polypeptides useful in screening for the presence of one or more polypeptides having a selected binding or enzymatic activity. The library polypeptides include (a) regions A, AB, B, C, CD, D, E, EF, F, and G having wildtype amino acid sequences of a selected native fibronectin Type 3 polypeptide or polypeptides, and (b) loop regions AB, CD, and EF having selected lengths (Bottom Loops). The Fn3 may also have loop regions BC, DE, and FG having wildtype amino acid sequences, having selected lengths, or mutagenized amino acid sequences (Top Loops).

Abstract: The present invention relates to a method for in vitro producing polynucleotides encoding human germline antibody V-regions. Also disclosed is a library of human germline antibody V-region genes.

Abstract: The present invention relates to a polymorphic MRP-1 polynucleotide, genes or vectors comprising the polynucleotides and a host cell genetically engineered with the polynucleotide or gene. Also provided are methods for producing molecular variant polypeptides, cells capable of expressing a molecular variant polypeptide and to a polypeptide encoded by the polynucleotide or the gene or obtainable by the method or cells produced herein. Also provided is an antibody to the polypeptide, a transgenic animal, and to a solid support comprising one or a plurality of the provided polynucleotides, genes, vectors, polypeptides, antibodies or host cells. Furthermore, methods of identifying a polymorphism, identifying and obtaining a pro-drug or drug or an inhibitor are also provided. In addition, the invention relates to methods for producing of a pharmaceutical composition, diagnosing a disease and, detection of the polynucleotide.

Abstract: The present invention relates to a product comprising a solid substrate and a moiety of formula (I) linked thereto: wherein X, X? and R are as defined herein. The product is useful for immobilising target molecules such as molecules of biochemical interest to solid substrates for numerous applications, such as affinity chromatography, ELISA, biotechnological assay techniques and solid phase peptide synthesis.

Abstract: The present disclosure provides aldehyde-tagged immunoglobulin (Ig) polypeptides that can be converted by a formylglycine-generating enzyme to produce a 2-formylglycine (FGly)-modified Ig polypeptide. An FGly-modified Ig polypeptide can be covalently and site-specifically bound to a moiety of interest to provide an Ig conjugate. The disclosure also encompasses methods of production of such aldehyde-tagged Ig polypeptides, FGly-modified Ig polypeptides, and Ig conjugates, as well as methods of use of same.

Abstract: The present invention relates to the production of antibody libraries. In particular, the present invention relates to the use of integrating retroviral vectors to generate libraries comprising a plurality of combinations of antibody light chains and heavy chains. The present invention thus provides improved methods of generating and screening antibody libraries comprising large numbers of unique antibodies.

Abstract: The present invention provides combinations of specific binding proteins, such as immunoglobulins, that are designed to be true combinations, essentially all components of the combination being functional and compatible with each other. The invention further provides a method for producing a composition comprising at least two different proteinaceous molecules comprising paired variable regions, the at least two proteinaceous molecules having different binding specificities, comprising paired variable regions, at least two proteinaceous molecules having different binding specificities, comprising contacting at least three different variable regions under conditions allowing for pairing of variable regions and harvesting essentially all proteinaceous molecules having binding specificities resulting from the pairing.

Abstract: Methods and compositions for identifying D-peptidic compounds that specifically bind target proteins are provided. Aspects of the methods include screening libraries of 20 residue or more L-peptidic compounds for specific binding to 40 residue or more D-target proteins. Once a L-peptidic compound has been identified that specifically binds to the D-target protein, the D-enantiomer of that compound may be produced.

Abstract: The present invention provides novel methods for producing nucleic acid fragment libraries that express highly diverse peptides or protein domains and, in particular, methods for producing nucleic acid fragment libraries wherein the nucleic acid fragments of the libraries are derived from two or more diverse characterized genomes.

Abstract: The transformation yield of electroporation is increased by using higher DNA concentrations and DNA affinity purification. Fusion proteins of a viral coat protein variant and a heterologous polypeptide are useful in phage display systems.

Abstract: The present invention is generally directed to novel functionalized biomolecules and methods for generating such biomolecules. Biomolecules may generally include nucleic acids, peptides, multicomponent molecular complexes and/or any other molecular products that may be produced by living organisms. The present invention is further directed to cells and/or organisms manipulated to produce such functionalized biomolecules. The cells contemplated by the present invention include both prokaryotic as well as eukaryotic cells. The functionalized biomolecules are produced via materials introduced into the cell using standard molecular biology techniques or are incorporated within the genomic nucleic acid of a cell by standard recombination techniques. Further contemplated is the use of such cells for sequestration of target molecules within the cells.

Abstract: The present invention provides high throughput assays for identifying compounds that modulate a contractile function, as well as devices suitable for use in these assays.

Abstract: The present disclosure enables collections of variable heavy chain and variable light chain pairs comprising, in part, germline protein sequences that are pre-selected for functional properties relevant to developability, wherein the collections may be used to select against any antigen using, for example, phage display.

Abstract: Magnetic nanoparticles and methods for their use in detecting biological molecules are disclosed. The magnetic nanoparticles can be attached to nucleic acid molecules, which are then captured by a complementary sequence attached to a detector, such as a spin valve detector or a magnetic tunnel junction detector. The detection of the bound magnetic nanoparticle can be achieved with high specificity and sensitivity.

Abstract: The present invention describes an improved method of screening of anti HCV agents that may have an efficacy for treatment of hepatitis C virus. The invention includes cryogenic hepatocyte bank, wherein the bank includes multiple hepatocytes collected from multiple HCV patients and the hepatocyte bank includes more than one genotype of HCV. The method involves the isolation and cryopreservation of HCV infected hepatocytes from multiple infected individuals. The isolated and cryopreserved hepatocytes are stored in a cryopreservation bank. These stored hepatocytes then are cultured in a culture medium, and anti-HCV screening of the hepatocytes is done by subjecting HCV infected hepatocytes in parallel to action of different anti-HCV compounds at various concentrations. Effective anti-HCV agents will lead to a decrease in HCV content in the cultures.

Abstract: Methods and compositions for the screening and isolation of ligand-binding polypeptides, such as antibodies. In some aspects, methods of the invention enable the isolation of intact soluble antibodies comprising a constant domain. Screening methods that employ genetic packages such as bacteria and bacteriophages enable high through-put identification of ligand binding molecules.

Abstract: Provided herein are methods of isolating a polynucleotide encoding a polypeptide such as an antibody with a desired property by way of mammalian display library screening and methods of generating a library of polynucleotides encoding polypeptides such as antibodies, wherein the polynucleotides collectively encode at least 109 different polypeptides. Also provided are kits for carry out the methods described herein, polynucleotides isolated by methods described herein, libraries encoding the antibody reservoir of different species including human, mouse, rabbit, and polypeptides encoded by the polynucleotides.

Abstract: The present invention relates to combinatorial gene expression libraries and methods for making these. Such libraries are useful in discovery of novel and/or enhanced metabolic pathways leading to the production of novel compounds for e.g., drug discovery and/or to the prosecution of known compounds in novel quantities or in novel compartments of the cells. The expression libraries in particular are composed of host cells capable of co-ordinated and controllable expression of large numbers of heterologous genes in the host cells.

Abstract: Methods for performing surface-mediated protein delivery into living cells, and fabricating protein-transfected cell cluster arrays are provided. The method comprises providing a protein-containing mixture; depositing said protein-containing mixture onto a surface at defined locations; affixing the protein-containing mixture to the surface as microspots; and plating cells onto the surface in sufficient density and under conditions for the proteins to be delivered into the cells. The protein-containing mixture comprises any suitable amino acid sequence, including peptides, proteins, protein-domains, antibodies, or protein-nucleic acid conjugates, etc., with a carrier reagent. Protein-transfected cell arrays may be used for rapid and direct, screening of protein or enzymatic functions or any given intracellular protein interaction in the natural environment of a living cell, as well as for high-throughput screening of other biological and chemical analytes, which affect the functions of these proteins.

Abstract: Methods for performing surface-mediated protein delivery into living cells, and fabricating protein-transfected cell cluster arrays are provided. The method comprises providing a protein-containing mixture; depositing said protein-containing mixture onto a surface at defined locations; affixing the protein-containing mixture to the surface as microspots; and plating cells onto the surface in sufficient density and under conditions for the proteins to be delivered into the cells. The protein-containing mixture comprises any suitable amino acid sequence, including peptides, proteins, protein-domains, antibodies, or protein-nucleic acid conjugates, etc., with a carrier reagent. Protein-transfected cell arrays may be used for rapid and direct, screening of protein or enzymatic functions or any given intracellular protein interaction in the natural environment of a living cell, as well as for high-throughput screening of other biological and chemical analytes, which affect the functions of these proteins.

Abstract: Provided is a process for creating a 3D metabolically active microtissue perfused with living microvessels which have a direct fluidic connection with neighboring microfluidic channels. The process comprises preparing a template comprising a plurality of channels, and creating a network within said channels, said network comprising microfluidic channels, metabolically active living microvessels, and microtissues. The microvessels can sprout from said microvessels and/or form within the microtissue in response to a stimulus applied from said microfluidic channels or stimulus derived from the said tissues. In another embodiment, a device is provided comprising a supportive structure, one or more microfluidic channels, one or more microtissue compartments, and one or more microvessels, whereby the microvessels connect said microfludic channels and microtissue and perfuse the microtissue to deliver fluid from the microfluidic channels to the microtissues.

Abstract: The present invention relates to a method for in vivo molecular evolution of antibody function. According to the present invention, a nucleic acid encoding a CDR that is normally contained in a framework (the “original framework”), which differs from a selected master framework, is amplified from an immunoglobulin gene and is inserted into a nucleic acid encoding the selected master framework. The invention further provides an antibody library, such as a phage display library, and methods of making the same.

Abstract: The present invention relates generally to methods for producing normalized nucleic acid libraries in which each member of the library can be isolated with approximately equivalent probability. In particular, the present methods comprise subtractive hybridization of a nucleic acid library with haptenylated (e.g., biotinylated, avidinated or streptavidinated) nucleic acid molecules that are complementary to one or more of the nucleic acid molecules of the library, such that the variation in the abundances of the individual nucleic acid molecules in the library is reduced. The invention also relates to production of normalized nucleic acid libraries (particularly cDNA libraries) in which contaminating nucleic acid molecules have been reduced or eliminated, and to normalized nucleic acid libraries produced by such methods.

Abstract: The invention relates to a method of diagnosing or monitoring major depressive disorder.

Abstract: Recombinant adeno-associated viral (AAV) capsid proteins are provided. Methods for generating a library of recombinant adeno-associated viral capsid proteins are also provided.

Abstract: The invention relates to a nucleic acid comprising the following contiguous elements arranged in the 5 prime to 3 prime direction; a promoter; a selectable marker; a cloning site for receipt of a nucleic acid segment, said segment comprising a candidate miRNA target sequence; and a poly adenylation signal, said elements arranged such that a transcript directed by said promoter comprises said selectable marker, said candidate miRNA target sequence, and said poly adenylation signal in that order. Suitably the miRNA test sequence is or is derived from a 3?UTR. The invention also relates to methods for making and screening libraries.

Abstract: The present invention concerns methods and compositions for in vivo and in vitro targeting. A large number of targeting peptides directed towards human organs, tissues or cell types are disclosed. The peptides are of use for targeted delivery of therapeutic agents, including but not limited to gene therapy vectors. A novel class of gene therapy vectors is disclosed. Certain of the disclosed peptides have therapeutic use for inhibiting angiogenesis, inhibiting tumor growth, inducing apoptosis, inhibiting pregnancy or inducing weight loss. Methods of identifying novel targeting peptides in humans, as well as identifying endogenous receptor-ligand pairs are disclosed. Methods of identifying novel infectious agents that are causal for human disease states are also disclosed. A novel mechanism for inducing apoptosis is further disclosed.

Abstract: A biosensor for use in detecting the presence of diseases, the biosensor comprising a detector for detecting a presence of at least one marker indicative of a specific disease. A method of determining efficacy of a pharmaceutical for treating a disease or staging disease by administering a pharmaceutical to a sample containing markers for a disease, detecting the amount of at least one marker of the disease in the sample, and analyzing the amount of the marker in the sample, whereby the amount of marker correlates to pharmaceutical efficacy or disease stage. Markers for gynecological disease selected from the list in Table 8. An immuno-imaging agent comprising labeled antibodies, whereby the labeled antibodies are isolated and reactive to proteins overexpressed in vivo. Informatics software for analyzing the arrays of claim 17, the software including analyzing means for analyzing the arrays.

Abstract: The present invention relates to expression cassettes libraries of expression vectors comprising the same, wherein each vector comprises at least one gene of interest and a promoter operatively linked thereto wherein each promoter comprises a nucleic acid, whose sequence is randomly mutated with respect to that of another in the library and cells comprising the same. Methods utilizing either the libraries or cells of this invention, in optimizing gene expression, protein expression, or optimized gene or protein delivery are described.

Abstract: Libraries of immunoglobulins which each have one or more amino acid modifications in at least one structural loop region of such immunoglobulins, where the modified loop region specifically binds to an epitope of an antigen to which an unmodified immunoglobulin does not significantly bind.

Abstract: The invention provides a method for the expression and subsequent screening of DNA libraries, particularly synthetic, genomic, and cDNA libraries, in filamentous fungal hosts. In particular, the invention provides vectors, host strains, and a method for the expression and screening of complex DNA libraries, including, but not limited to, combinatory (combinatorial) libraries expressing one, two or more variable constituents and/or prepared from two or more sublibraries (e.g., for the expression and screening of immunoglobulin (including fragments and derivatives of whole immunoglobulin proteins) and other receptor or complex DNA libraries or libraries of libraries). The invention is useful for the expression and screening for a large variety of proteins and protein complexes, including human proteins. The present invention also relates to novel fungal protease sequences.