Abstract: This invention relates to a single cell assay for determining the effect of chromosomal contact on the transcriptional activity of genes of interest in a cell and to methods of silencing gene expression in a cell by way of perturbing gene regulatory elements which are engaged in chromosomal contact.

Abstract: A sustained culture of isolated avian gonocytes is provided, as well as a method of making and using the same. A chimeric avian containing an isolated gonocyte and a transgenic avian produced using the chimeric avian are also provided. The cell and method may be employed to make, among other things, transgenic avian that produce a heterologous protein, e.g., a therapeutic protein.

Abstract: The invention provides for compositions and methods for identifying and validating modulators of cell fate, such as such as maintenance, cell specification, cell determination, induction of stem cell fate, cell differentiation, cell dedifferentiation, and cell trans-differentiation. The invention relates to reporter nucleic acid constructs, host cells comprising such constructs, and methods using such cells and constructs. The invention relates to methods for making cells comprising one or more reporter nucleic acid constructs using fluorogenic oligonucleotides. The methods relate to high throughput screens.

Abstract: Devices, systems, and methods for continuous cell culture and other reactions are generally described. In some embodiments, chambers (e.g., cell growth chambers) including at least a portion of a wall formed of a flexible member are provided. A retaining structure can be incorporated outside and proximate to the chamber such that when liquid is added to the chamber, the flexible member is consistently and predictably deformed, and a consistent volume of liquid is added. The flexible member can be formed of, in some embodiments, a gas-permeable medium. In some embodiments, reaction chambers can be arranged in a fluidic loop, and a bypass channel can be used to introduce and/or extract fluid from the loop without affecting loop operation.

Abstract: The present invention notably relates to novel recombinant telomerase reverse transcriptases, nucleic acid molecules coding them, cells comprising said nucleic acid molecule and use of these cells for the production of substance of interest.

Abstract: Methods for producing reassortant viruses are provided wherein the transcription and/or translation of the hemagglutinin and/or neuraminidase genes are suppressed.

Abstract: The present invention relates to nucleic acids encoding peptides capable of binding to actin. The nucleic acids encoding the peptides are useful in methods for detecting actin in vitro or in living cells.

Abstract: The invention provides a process for generating an avian cell line of duck origin by a process comprising: —cultivating embryonic avian cells in cell culture medium, preferably comprising fetal calf serum (FBS) for more than 40 passages while reducing the concentration of FBS to 1-2% vol/vol FBS, —transferring passaged cells into cell culture medium having 0% FBS, —resulting in the generation of a non-embryonic avian cell line suitable for non-adherent growth, i.e. for growth in suspended culture.

Abstract: The present invention relates to Protoxin-II variants, polynucleotides encoding them, and methods of making and using the foregoing.

Abstract: Embodiments of the present invention relate to a spontaneously immortalized avian cell line, designated ZS-1. Immortalized avian cell line, ZS-1 is derived from primary chicken embryo fibroblasts (CEF). The ZS-1 cell line is free of endogenous retroviruses, including Avian Leukosis Viruses (ALV), and particularly ALV sub-group E. Moreover, the ZS-1 cell line susceptible to all subgroups of ALV, including subgroup E. Cells of the ZS-1 cell line and sub-clones thereof may be used for inter alia the production of viral agents, including recombinant viral agents, expression of recombinant proteins, and diagnostic assays.

Abstract: A sustained culture of isolated avian gonocytes is provided, as well as a method of making and using the same. A chimeric avian containing an isolated gonocyte and a transgenic avian produced using the chimeric avian are also provided. The cell and method may be employed to make, among other things, transgenic avian that produce a heterologous protein, e.g., a therapeutic protein.

Abstract: The present invention relates to chemical compounds, methods for their discovery, and their therapeutic and research use. In particular, the present invention provides antiviral and antimicrobial lectin compounds and methods of their use.

Abstract: The present invention relates to a method for production of continuous cell lines comprising providing living cells of an animal or a human, irradiating said cells with UV light, proliferating said cells and selecting multiplying cells as cells of a continuous cell line.

Abstract: The present invention relates to methods for transfecting cells. In particular, the present invention relates to methods of transfecting primordial germ cells in avians, and to methods of breeding avians with modified traits.

Abstract: The present invention provides a method for improving pancreatic function in a subject in need thereof, the method comprising administering to the subject STRO-1+ cells and/or progeny cells thereof and/or soluble factors derived therefrom. The method of the invention is useful for treating and/or preventing and/or delaying the onset or progression of a disorder resulting from or associated with pancreatic dysfunction, e.g., resulting from abnormal endocrine or exocrine function of the pancreas.

Abstract: Provided is a single construct combining a sequence encoding an RNAi molecule, a sequence encoding a reporter, and a target sequence specific for the RNAi molecule. The construct can be used to determine the potency of the encoded RNAi molecule in a direct and unbiased way. These results can be used to inform the design of potent RNAi molecules of various types and can be extended to several other applications, including: (1) generation of tiled libraries comprising every possible RNAi molecule-encoding sequence for a given gene target; (2) large-scale parallel validation of RNAi molecules targeting many genes to generate validated RNAi molecule-encoding libraries; (3) experimental comparison of design algorithms and strategies; and (4) investigation of RNAi biology in target site mutagenesis assays by screening pools containing single nucleotide changes in target sites and/or in the RNAi molecule to identify the most relevant sequence characteristics of potent RNAi-target site predictions.

Abstract: Provided herein are methods to generate and screen peptides that exhibit drug like stabilities in vitro and in vivo. By selecting for enzyme resistance, Applicants are able to derive peptides that are not only stable to a broad spectrum of proteases, but also stable to other drug processing enzymes such as cytochrome P450s. This approach provides a general method to the rapid development of highly stable peptides for therapeutic development and diagnosis. The peptides are further modified for oral bioavailability.

Abstract: The present invention is directed to the biosynthetic pathway for a nonribosomal peptide synthetase (NRPS) derived drug and analogs thereof. The invention also discloses polynucleotide sequences useful for heterologous expression in a convenient microbial host for the synthesis of the NRPS derived drug.

Abstract: An inactive CRISPR/Cas system-based fusion protein and its applications in gene editing are disclosed. More particularly, chimeric fusion proteins including an inCas fused to a DNA modifying enzyme and methods of using the chimeric fusion proteins in gene editing are disclosed. The methods can be used to induce double-strand breaks and single-strand nicks in target DNAs, to generate gene disruptions, deletions, point mutations, gene replacements, insertions, inversions and other modifications of a genomic DNA within cells and organisms.

Abstract: This invention relates to a mammalian artificial chromosome vector, which retains a human chromosome 7 fragment comprising human cytochrome P450 genes and is transmittable to progeny, wherein the human chromosome 7 fragment retains a region of approximately 1 Mb±500 Kb in size comprising at least a human CYP3A gene cluster, which region is located between chromosome markers AC004922 and AC073842, and to a non-human mammalian animal retaining the vector.

Abstract: Methods are described for the delivery of one or more small interfering RNAs (siRNAs) to a eukaryotic cell using a bacterium. Methods are also described for using this bacterium to regulate gene expression in eukaryotic cells using RNA interference, and methods for treating an inflammatory disease or disorder. The bacterium includes one or more siRNAs or one or more DNA molecules encoding one or more siRNAs. Vectors are also described for use with the bacteria of the invention for causing RNA interference in eukaryotic cells.

Abstract: The present invention relates to immortalized avian cell lines suitable for production of biologicals or viruses for vaccination. In particular, the cell lines are derived from primary cells which are transformed with at least two viral or cellular genes, one of which causes cell cycle progression whereas the other interferes with innate protective mechanisms of the cell induced by dysregulated replication. The invention moreover relates to the production of said immortalized cell lines and their use for producing biologicals or viruses for vaccination.

Abstract: Methods are described for the delivery of one or more small interfering RNAs (siRNAs) to a eukaryotic cell using a bacterium. Methods are also described for using this bacterium to regulate gene expression in eukaryotic cells using RNA interference, and methods for treating an inflammatory disease or disorder. The bacterium includes one or more siRNAs or one or more DNA molecules encoding one or more siRNAs. Vectors are also described for use with the bacteria of the invention for causing RNA interference in eukaryotic cells.

Abstract: The present invention relates to a cell for producing a secreted protein comprising a polynucleotide comprising a nucleic acid sequence encoding a fast cycling cdc42 mutant and a polynucleotide comprising a nucleic acid sequence encoding a secreted protein. It also relates to a method for producing said cell and to a method for producing a secreted protein using said cell.

Abstract: The invention provides an isolated H3 equine influenza A virus, as well as methods of preparing and using the virus, and genes or proteins thereof.

Abstract: The present invention relates to the production of avian induced pluripotent stem cells from non-pluripotent somatic cells, including embryonic fibroblasts and adult somatic cells. In this method, avian (including quail or chicken) somatic cells are reprogrammed into a state closely resembling embryonic stem cells including the expression of key stem cell markers alkaline phosphatase, etc. by transfecting/transducing the non-stem cells with genes (preferably using a non-integrating vector as otherwise described herein or alternatively an integrating vector, such a lentiviral vector, retroviral vector or inducible lentiviral vector, among others) which express at least nanog, Lin28 and cMyc. In preferred aspects of the invention, the transfected/transduced vectors express nanog, Lin28, cMyc, Oct 4 (POU5F1 or PouV), SOX2 and KLF4. The induced stem cells which are produced contribute to all 3 germ layers, the trophectoderm and in certain aspects, the gonad in chimeric offspring.

Abstract: Provided is a gene targeting vector that enables highly efficient gene targeting. The gene targeting vector has a structure comprising a positive selection marker flanked by a DNA homologous to a 5?-upstream region of a target site and a DNA homologous to a 3?-downstream region of the target site, wherein a splice acceptor site and a DNA sequence allowing for bicistronic expression are added 5?-upstream of the positive selection marker, and another splice acceptor site is also added 5?-upstream of the DNA homologous to the 5?-upstream region of the target site.

Abstract: Transgenes encoding exogenous antibodies are stably integrated into donor cells and are present in the somatic tissue of chimeric birds. The transgenes encode exogenous antibodies and are preferably expressed in the oviduct for collection in the egg. Tissue specificity is provided by selecting the content of the transgene accordingly. Birds whose genome is comprised of transgene-derived exogenous antibody-encoding DNA express exogenous antibodies having desirable chemical properties with increased therapeutic utility compared to antibodies derived from bacterial expression systems.

Abstract: The present invention relates to a method for improving viability and/or stress tolerance of viable biological material and using the said material comprising applying hydrostatic pressure to said biological material; keeping the said viable biological material at the hydrostatic pressure for a predetermined time period; releasing the hydrostatic pressure; and using the said material for any desired purpose in accordance with any useful protocol. The usage of the said biological material incorporates any techniques, protocols that are applicable in the field of assisted reproductive techniques, biotechnical and/or biotechnological manipulations.

Abstract: This invention relates to the field of biotechnology or genetic engineering. Specifically, this invention relates to the field of gene expression. More specifically, this invention relates to novel substitution mutant receptors and their use in a nuclear receptor-based inducible gene expression system and methods of modulating the expression of a gene in a host cell for applications such as gene therapy, large scale production of proteins and antibodies, cell-based high throughput screening assays, functional genomics and regulation of traits in transgenic organisms.

Abstract: This invention relates to the field of therapeutics. Most specifically, the invention provides methods of generating conditionally expressing one or more proteins under the control of a gene expression modulation, system in the presence of activating ligand and uses for therapeutic purposes in animals. The vector may be provided to treat or prevent disease.

Abstract: The present invention relates to fluorescent proteins, in particular green fluorescent proteins (GFPs), with increased activity in cells, and thus increased signal strength. A further aspect of the present invention relates to the use of peptides for increasing the expression and/or stability of a protein in a cell.

Abstract: The present invention provides a novel fusion polypeptide containing a catalytic portion of NPP1 fused to a targeting moiety, nucleic acids encoding the fusion polypeptide, a vector containing the nucleic acid integrated thereinto, a host cell transformed with the vector and pharmaceutical compositions comprising the fusion polypeptide.

Abstract: A transgenic avian containing in its genome an exogenous nucleotide sequence which includes a promoter component and a vector with reduced promoter interference wherein the exogenous nucleotide sequence is integrated into the genome and the avian.

Abstract: The present invention is transgenic chickens obtained from long-term cultures of avian PGCs and techniques to produce and transgenic birds derived from prolonged PGC cultures. In some embodiments, these PGCs can be transfected with genetic constructs to modify the DNA of the PGC, specifically to introduce a transgene encoding an exogenous protein. When combined with a host avian embryo by known procedures, those modified PGCs are transmitted through the germline to yield transgenic offspring. This invention includes compositions comprising long-term cultures of PGCs that can be genetically modified by gene targeting, that can accept large amounts of foreign DNA and that contribute to the germline of recipient embryos.

Abstract: The present invention provides serum-free cell culture media formulations which are capable of supporting the in vitro cultivation of animal cells. The media comprise at least one nutrient of non-animal derivation, such as at least one plant peptide and/or at least one non-animal or plant lipid and/or fatty acid. The media may further optionally comprise an enzymatic digest or extract of yeast cells. The present invention also provides methods of cultivating animal cells in vitro using these cell culture media formulations. In addition, the media of the present invention can be used for growth of animal cells for virus production.

Abstract: The present disclosure provides complexes comprising an FGF-10 portion and a heterologous protein or peptide, as well as methods of using such complexes.

Abstract: The present invention provides compositions comprising an isolated mixture of recombinant human NaGlu proteins in which a substantial amount of the NaGlu proteins in the mixture has increased levels of phosphorylated mannose that confer the proteins to be efficiently internalized into human cells. The present invention also provides methods of producing such mixture of NaGlu proteins, vectors used in transgenesis and expression, host cells harboring such vectors, and methods of isolating and purifying the mixture of NaGlu proteins. The invention further provides methods of treating NaGlu associated diseases.

Abstract: The present invention relates to compositions and methods for preparing cells from avian embryos. The invention also relates to cultures of such cells and the uses thereof, particularly for producing viruses such as MDV. The invention also relates to methods for the preparation of vaccines using such cells or viruses.

Abstract: The present invention relates to cellular proteins that are involved in toxicity and infection or are otherwise associated with the life cycle of one or more pathogens.

Abstract: The present invention provides a method for preparing a non-adenoviral target virus or target proteins utilizing a potent expression cell line having stably integrated into its genome a gene encoding a specific heterologous regulator protein.

Abstract: This invention relates to immortalized avian cells, and to the use of these cells for the production of viruses. The cells according to the invention are particularly useful for the production of recombinant viral vectors which can be used for the preparation of therapeutic and/or prophylactic compositions for the treatment of animals and more particularly humans.

Abstract: The present invention encompasses PRLR binding proteins. Specifically, the invention relates to antibodies that are chimeric, CDR grafted and humanized antibodies. Preferred antibodies have high affinity for hPRLR and neutralize hPRLR activity in vitro and in vivo. An antibody of the invention can be a full-length antibody or an antigen-binding portion thereof. Methods of making and methods of using the antibodies of the invention are also provided. The antibodies, or antibody portions, of the invention are useful for detecting hPRLR and for inhibiting hPRLR activity, e.g., in a human subject suffering from a disorder in which hPRLR activity is detrimental. Also included in the invention are anti-PRLR antibody drug conjugates (ADCs).

Abstract: The present invention relates to antibodies against human collagen II, polypeptides and polynucleotides encoding human collagen II antibodies or fragments thereof, and methods of making and using the foregoing.

Abstract: The present invention relates to immunostimulatory oligodeoxynucleotides, vectors and vaccines comprising such oligodeoxynucleotides, to their use as a medicament, to their use in preventing or combating infectious disease, to methods for the detection of such oligodeoxynucleotides and to cells to be used in these method.

Abstract: The present invention relates generally to a method of modifying gene expression and to synthetic genes for modifying endogenous gene expression in a cell, tissue or organ of a transgenic organism, in particular a transgenic animal or plant. More particularly, the present invention utilizes recombinant DNA technology to post-transcriptionally modify or modulate the expression of a target gene in a cell, tissue organ or whole organism, thereby producing novel phenotypes. Novel synthetic genes and genetic constructs which are capable of repressing delaying or otherwise reducing the expression of an endogenous gene or target gene in an organism when introduced thereto are also provided.

Abstract: The present invention provides a method of artificially repressing gene expression, which is simpler to design than conventional methods (the RNAi, ribozyme and antisense methods) and which allows for easier confirmation of the effect. A method of inhibiting the translation reaction of a target gene, comprising cutting out a part of the poly(A) tail and/or 3?-terminal sequence of the target mRNA is provided.

Abstract: The use of a composition including at least one permeabilized nucleus of a first cell, or at least one permeabilized first cell including the nucleus and an extract of female germinal cells, or eggs, of a multicellular organism, the eggs being blocked in the metaphase II of meiosis, the extract including EGTA, for carrying out a method for obtaining pluripotent stem cells, or tissues derived from the pluripotent stem cells, or of cloning, provided that the process is not for cloning human beings.

Abstract: The present invention relates to a polypeptide binding to a chymase (EC 3, 4, 21,39), wherein the polypeptide comprises or consists of an amino acid sequence selected from the group consisting of: (a) GVTLFVALYDY(X1)A(X2)(X3)(X4)(X5) (X6)LSFHKGEKFQIL(X7 (X8)(X9)(X10) (X11)(X12)G(X13)(X14)WEARSLTTGETGYIPSNYVAPVDSIQ (SEQ ID NO: 1), wherein (X1) is R, N, Q, E, K, H, S, T, C, or D; (X2) is E, T, D, Q, L, P, A, S, C, M, N, E, G, A, V or I; (X3) is R, T, H, N, K, S, C, N or Q; (X4) is S, W, T, C, N, Q, For Y; (X5) is T, H, L, F, C, S, M, N, Q, R, K, G, A, V, I, P, Y or W; (X6) is D, Q, H, E, S, T, C, N, R or K; (X7) is D, N, R, E, Q, S, T, C, K or D; (X8) is M, W, G, F, A, S, T, C, S, N, Q, Y, V, L, I or P; (X9) is T, H, S, D, C, N, Q, R, K, E or absent; (X10) is V, T, Q, G, A, L, I, P, S, C, M, N or absent; (X11) is P, A, D, G, K, V, L, I, E, R, M, H or absent; (X12) is N, V, P, I, E, T, S, A, G, L, C, M, Q or D; (X13) is D, E, T, P, G, A, V, L, I, S, C, M, N or Q, and (X14) is W, Y, L, G, A, V, I, P, M, or F; (b)

Abstract: Nucleic acid and polypeptide sequences corresponding to FLAT, a partly cytosolic variant of the intracellular anandamide-degrading enzyme, fatty acid amide hydrolase-1 (FAAH-1), are provided. FLAT lacks amidase activity but binds the endocannibinoid anandamide and facilitates its transport into cells. A chemical scaffold for the inhibition of anandamide transport is identified. Compositions of the invention prevent anandamide internalization in vitro, interrupt anandamide deactivation in vivo, and cause profound CB1 cannabinoid receptor-mediated analgesia in a mouse model of inflammatory pain. Accordingly, the invention also provides methods, and pharmaceutical compositions for treating conditions in which the modulation of anandamide transport would be of benefit.