Abstract: The invention provides a method for the improved generation of genetically modified cells in vitro, in order to obtain a population of effector cells with immunotherapeutic activity and methods of using such cells in protocols for adoptive cell therapy. The invention further provides non-viral genetically modified cells, cell populations and cell cultures and the use thereof in the treatment or prevention of diseases and disorders.

Abstract: The present invention provides a method for inducing an inversion of normal blood coagulation factor VIII (F8) gene, a method for correcting an inversion of blood coagulation factor VIII gene in which the inversion has occurred, and a Hemophilia A patient-derived induced pluripotent stem cell in which the inversion is corrected, constructed using the same. The method of the present invention effectively reproduces the inversion of intron 1 and intron 22 of the F8 gene, which is responsible for the majority of severe hemophilia A, and thereby may be effectively used for studying the development mechanism of hemophilia A and as a research tool for screening therapeutic agents. The inversion-corrected induced pluripotent stem cell constructed according the method of the present invention enables an efficient and fundamental treatment for hemophilia A by restoring a genotype in which mutation has occurred to a wild type-like state, without limitation via normal gene or protein delivery.

Abstract: The invention relates in aspects to hybrid RNAs lacking a poly-A tail and nucleic acid vectors for expressing the RNA. The hybrid RNAs in some instances have a stabilizing triple helical structure. Related methods for expressing RNA in vivo and in vitro are also disclosed.

Abstract: The invention relates, in part, to a library of chimeric proteins, each chimeric protein including a mini-protein between about eight and about forty amino acids long, wherein the mini-protein has a single disulfide bond formed by a pair of invariant cysteines and has only two cysteines. The chimeric protein also includes at least a portion of an outer surface protein of a genetic package, wherein the chimeric protein is displayed on the outer surface of the genetic package. The invention also includes, in part, a mixture of nucleic acids that encode a library of the invention. The invention also includes, in part, a process for identifying proteins with a desired binding activity against a target, the process including screening a library of chimeric proteins of the invention; and identifying the chimeric protein. The invention, in part, also includes chimeric proteins expressed by a library of the invention.

Abstract: The present invention concerns double-stranded NF-?B decoy oligodeoxynucleotide (NF-?B dsODN) molecules that contain a core sequence capable of specific binding to an NF-?B transcription factor. In a particular aspect, the invention concerns NF-?B decoy molecules that preferentially bind p50/p65 and/or cRel/p50 heterodimers over p50/p50 homodimers. In another aspect, the invention concerns NF-?B decoy molecules with improved binding affinity to p65.

Abstract: A plurality of genes modulated by estrogen or other agents, such as hormones or combinations of hormones, in various types of tissue is described. One embodiment of the disclosure relates to a plurality of genes, which demonstrates certain patterns of expression differing qualitatively or quantitatively, with and without exposure to estrogen and/or other hormone compositions. Methods of using these genes in identifying candidate agents that exert at least some of the biological effects of estrogen and/or other hormone, and pharmaceuticals and related therapies also is disclosed. The use of the plurality of genes in methods of monitoring, in gene chips and in kits also is disclosed.

Abstract: Provided are methods for the identification of novel genes involved in a variety of cellular processes, including retinal degeneration, retinal disease, cancer, memory and learning, amylotropic lateral sclerosis, and methods for the identification of the function of a variety of genes and gene fragments of unknown function. The genes thus identified, as well as the compositions used in the identification methods, are also provided.

Abstract: The present invention provides a number of gene markers whose expression is altered in various gliomas. In particular, by examining the expression these markers, one can accurately classify a glioma as glioblastoma multiforme (GM), anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO) or oligodendroglioma (OL). The diagnosis may be performed on nucleic acids, for example, using a DNA microarray, or on protein, for example, using immunologic means. Also disclosed are methods of therapy.

Abstract: A combinatorial library of fluorescent compounds useful as organelle-specific probes are produced by reacting an aldehyde with a 2- or 4-methylpyridinium salt.

Abstract: This invention provides high unit density arrays of microparticles and methods of assembling such arrays. The microparticles in the arrays may be functionalized with chemical or biological entities specific to a given target analyte. The high unit density arrays of this invention are formed on chips which may be combined to form multichip arrays according to the methods described herein. The chips and/or multichip arrays of this invention are useful for chemical and biological assays.

Abstract: Methods for preparing a glycopeptide are disclosed. The methods comprise the steps of selecting a protected glycopeptide of the formula A1-A2-A3-A4-A5-A6-A7, wherein the groups A1 to A7 comprise the heptapeptide structure of naturally occurring vancomycin; at least A4 is linked to a glycosidic group which has a hexose residue linked to A4; and the protected glycopeptide has no free amino or carboxyl groups and has a free primary hydroxyl group only at the 6-position of said hexose residue. The protected glycopeptide is contacted with a compound of the formula ArSO2G where Ar is an aryl group and G is a leaving group under conditions effective to allow reaction of said free primary hydroxyl group to form a glycopeptide sulfonate ester; and the glycopeptide sulfonate ester is contacted with a nucleophile under conditions effective to allow displacement of a sulfonate group to produce a substituted glycopeptide.

Abstract: There is described a method of isolating nucleotide sequences encoding target peptides from DNA libraries using DNA binding proteins to link the peptide to the sequence which encodes it. DNA libraries are prepared from cells encoding the protein of interest, or from synthetic DNA, and inserted into, or adjacent to, a DNA binding protein in an expression vector to create a chimeric fusion protein. Incorporation of the vector DNA into a carrier package, during expression of the chimeric fusion protein, results in the production of a peptide display carrier package (PDCP) displaying the DNA-bound fusion protein on the external surface of the carrier package. Employment of affinity purification techniques results in the PDCP particles containing sequences encoding the desired peptide to be selected and the desired nucleotide sequences obtained therefrom.

Abstract: The present invention provides novel compositions and methods for use in the treatment of cancer, specifically, in the treatment of chronic myelogenous leukemia (CML). The compositions contain antisense oligonucleotides that hybridize to Grb2 and Crk1 nucleic acids, the gene products of which are known to interact with the tumorigenic protein bcr-abl. Used alone, in conjunction with each other, and even in conjunction with antisense oligonucleotides directed to bcr-abl nucleic acids, these compositions inhibit the proliferation of CML cancer cells.

Abstract: Methods and compositions for reducing viral genome amounts in a target cell are provided. In the subject methods, the activity of a miRNA is inhibited in a manner sufficient to reduce the amount of viral genome in the target cell, e.g., by introducing a miRNA inhibitory agent in the target cell. Also provided are pharmaceutical compositions, kits and systems for use in practicing the subject methods. The subject invention finds use in a variety of applications, including the treatment of subjects suffering from a viral mediated disease condition, e.g., an HCV mediated disease condition.

Abstract: Methods of detecting components of interest, e.g., nucleic acids and sugars, are provided. The methods comprise contacting one or more nanowires comprising a functional group with a sample containing the component or components of interest. In one embodiment, the functional group comprises a hairpin oligonucleotide, e.g., a hairpin that changes conformation upon binding the component of interest, e.g., a nucleic acid. The change in conformation produces a change in charge that is detected. In another embodiment, the functional group comprises an enzyme, e.g., glucose oxidase, which produces a change in pH when glucose is present in a sample.

Abstract: A method is provided for treating hormone-regulated tumors (for example, breast and prostatic tumors) in mammals, including humans, by administration of an antisense ODN which is complementary to a portion of the gene encoding IGFBP-5. Using the Shionogi tumor model in vitro and in vivo, the administration of such an ODN was shown to reduce proliferation of tumor cells, and also to delay the progression to androgen independence. Thus, treatment of prostate cancer in mammals, including humans, and delay of the progression of prostate tumors to androgen independence is accomplished by administering to the mammal a therapeutically effective amount of an antisense oligodeoxynucleotide which is complementary to a portion of the nucleic acid sequence encoding IGFBP-5 and which hybridizes with such a sequence to inhibit expression of IGFBP-5. Specific antisense ODN's which are suitable for use in the method are GACCACGCTGATCACCAT (Seq. ID. No.

Abstract: Provided herein are sets of mass labels. Each mass label in a set includes 1) a mass marker moiety; 2) a mass normalisation moiety; and 3) a cleavable linker connecting the mass marker moiety to the mass normalisation moiety. Each mass marker moiety is characterised as having a mass different from that of all other mass marker moieties in the set as determined by mass spectrometry. Further, each mass normalisation moiety ensures that each mass label in the set has substantially the same mass as determined by mass spectrometry.

Abstract: Disclosed are transgenic animals and transfected cell lines expressing a protein associated with Alzheimer's Disease, neuroectodermal tumors, malignant astrocytomas, and glioblastomas. Also disclosed is the use of such transgenic animals and transfected cell lines to screen potential drug candidates for treating or preventing Alzheimer's disease, neuroectodermal tumors, malignant astrocytomas, and glioblastomas. The invention also relates to new antisense oligonucleotides, ribozymes, triplex forming DNA and external guide sequences that can be used to treat or prevent Alzheimer's disease, neuroectodermal tumors, malignant astrocytomas, and glioblastomas.

Abstract: The present invention provides for a transgenic animal model that constitutively expresses a protein encoded by the NPM-ALK gene in lymphoid tissue, and exhibits enhanced and accelerated development of a T cell lymphoproliferative disorder or B cell plasma cell tumor, together with the identification of cells transduced with the ALK tyrosine kinase gene or fusion proteins thereof, and methods for using this animal model and cells for screening compounds or treatments for antitumor activity. In preferred embodiments, the animal is a transgenic mouse that expresses a human NPM-ALK gene operably linked to human regulatory sequences, and the cells of the mouse have at least one copy of the NPM-ALK transgene, whereby the mouse constitutively expresses a protein encoded by the NPM-ALK transgene. The animals and cells of the invention are useful in the study of NPM-ALK-dependent lymphomagenesis and plasma cell tumors and in the development of treatments for these conditions.

Abstract: The present invention provides novel microfluidic devices and methods that are useful for performing high-throughput screening assays. In particular, the devices and methods of the invention are useful in screening large numbers of different compounds for their effects on a variety of chemical, and preferably, biochemical systems.