Abstract: Provided are methods for detecting or isolating circulating tumor cells (CTCs) in a subject. The methods may include detecting the expression of at least one epithelial mesenchymal transition (EMT) biomarker. Further provided are kits for detecting or isolating CTCs. The kits may include antibodies to at least one EMT biomarker. Further provided are methods of predicting the responsiveness of a subject to a cancer drug, methods of targeting delivery of a cancer drug in a subject, methods of providing a cancer prognosis to a subject, and methods for following the progress of cancer in a subject.

Abstract: Provided are methods for detecting or isolating circulating tumor cells (CTCs) in a subject. The methods may include detecting the expression of at least one epithelial mesenchymal transition (EMT) biomarker. Further provided are kits for detecting or isolating CTCs. The kits may include antibodies to at least one EMT biomarker. Further provided are methods of predicting the responsiveness of a subject to a cancer drug, methods of targeting delivery of a cancer drug in a subject, methods of providing a cancer prognosis to a subject, and methods for following the progress of cancer in a subject.

Abstract: The present invention includes a method, kits, and assays for identifying a human subject as having an increased risk of developing an autoimmune disease, or a human subject with multiple sclerosis caused by elevated soluble Interleukin 7 receptor (sIL7R), by obtaining a biological sample and detecting or measuring in the biological sample an amount of a soluble Interleukin-7 receptor (sIL7R) and an amount of an RNA Helicase DDX39B, whereby a lower expression of DDX39B and a higher secretion of sIL7R identifies the subject from which the biological sample was obtained as having an increased risk of developing an autoimmune disease, when compared to a human subject not having an autoimmune disease. The present invention also includes a method of modifying a treating of subjects based on the lower expression of RNA Helicase DDX39B alone or in combination with an increase in sIL7R.

Abstract: This disclosure provides compositions and methods for the isolation of cells that express c-MET, and in particular circulating tumor cells that express c-MET. The methods can include contacting a biological sample including a c-MET circulating tumor cell with an unbound complex including a capture binding species linked to a solid phase for a time sufficient to allow the unbound complex to bind an extracellular binding domain of the c-MET protein to form a bound complex, and subsequently isolating the bound complex. Compositions, systems, and kits adapted for use with these methods are also provided.

Abstract: Synthetic regulation of gene expression is provided. In some embodiments, synthetic regulatory constructs are provided. In some embodiments, a synthetic regulatory construct expresses a heterologous gene in a selected cell type. In some embodiments, methods of expressing a heterologous gene in a selected cell type are provided.

Abstract: Synthetic regulation of gene expression is provided. In some embodiments, synthetic regulatory constructs are provided. In some embodiments, a synthetic regulatory construct expresses a heterologous gene in a selected cell type. In some embodiments, methods of expressing a heterologous gene in a selected cell type are provided.

Abstract: Provided are methods for detecting or isolating circulating tumor cells (CTCs) in a subject. The methods may include detecting the expression of at least one epithelial mesenchymal transition (EMT) biomarker. Further provided are kits for detecting or isolating CTCs. The kits may include antibodies to at least one EMT biomarker. Further provided are methods of predicting the responsiveness of a subject to a cancer drug, methods of targeting delivery of a cancer drug in a subject, methods of providing a cancer prognosis to a subject, and methods for following the progress of cancer in a subject.

Abstract: Synthetic regulation of gene expression is provided. In some embodiments, synthetic regulatory constructs are provided. In some embodiments, a synthetic regulatory construct expresses a heterologous gene in a selected cell type. In some embodiments, methods of expressing a heterologous gene in a selected cell type are provided.

Abstract: Methods and compositions for generating novel nucleic acid molecules through targeted spliceosome mediated RNA trans-splicing that result in expression of a apoAI protein, an apoAI variant, the preferred embodiment referred to herein as the apoAI Milano variant, a pre-pro-apoAI or an analog of apoAI. The methods and compositions include pre-trans-splicing molecules (PTMs) designed to interact with a target precursor messenger RNA molecule (target pre-mRNA) and mediate a trans-splicing reaction resulting in the generation of a novel chimeric RNA molecule (chimeric RNA) capable of encoding apoAI, the apoAI Milano variant, or an analog of apoAI. The expression of this apoAI protein results in protection against vascular disorders resulting from plaque build up, i.e., atherosclerosis, strokes and heart attacks.

Abstract: Synthetic regulation of gene expression is provided. In some embodiments, synthetic regulatory constructs are provided. In some embodiments, a synthetic regulatory construct expresses a heterologous gene in a selected cell type. In some embodiments, methods of expressing a heterologous gene in a selected cell type are provided.

Abstract: Provided are methods for detecting circulating tumor cells (CTCs) in a subject. The methods may include detecting the expression of at least one epithelial mesenchymal transition (EMT) biomarker. Further provided are kits for detecting CTCs. The kits may include antibodies to at least one EMT biomarker. Further provided are methods of predicting the responsiveness of a subject to a cancer drug, methods of targeting delivery of a cancer drug in a subject, methods of providing a cancer prognosis to a subject, and methods for following the progress of cancer in a subject.

Abstract: The present invention provides, in certain aspects, a method of identifying a subject as having an increased risk of developing multiple sclerosis, comprising detecting in the subject the presence of a nucleotide variant in the interleukin 7 receptor alpha chain gene, whereby the presence of said variant identifies the subject as having an increased risk of developing multiple sclerosis.

Abstract: Methods and compositions for generating novel nucleic acid molecules through targeted spliceosome mediated RNA trans-splicing that result in expression of a apoAI protein, an apoAI variant, the preferred embodiment referred to herein as the apoAI Milano variant, a pre-pro-apoAI or an analogue of apoAI. The methods and compositions include pre-trans-splicing molecules (PTMs) designed to interact with a target precursor messenger RNA molecule (target pre-mRNA) and mediate a trans-splicing reaction resulting in the generation of a novel chimeric RNA molecule (chimeric RNA) capable of encoding apoAI, the apoAI Milano variant, or an analogue of apoAI. The expression of this apoAI protein results in protection against vascular disorders resulting from plaque build up, i.e., atherosclerosis, strokes and heart attacks.

Abstract: The present invention provides methods and compositions for generating novel nucleic acid molecules through targeted spliceosomal mediated RNA trans-splicing. The compositions of the invention include pre-trans-splicing molecules (PTMs) designed to interact with a SERPINA1 target precursor messenger RNA molecule (target pre-mRNA) and mediate a trans-splicing reaction resulting in the generation of a novel chimeric RNA molecule (chimeric RNA). In particular, the PTMs of the present invention include those genetically engineered to interact with SERPINA1 target pre-mRNA so as to result in correction of SERPINA1 genetic defects responsible for AAT deficiency. The PTMs of the invention may also comprise sequences that are processed out of the PTM to yield duplex siRNA molecules directed specifically to mutant SERPIN A1 mRNAs. Such duplexed siRNAs are designed to reduce the accumulation of toxic AAT protein in liver cells.

Abstract: The present invention provides methods and compositions for generating novel nucleic acid molecules through RNA trans-splicing that target a highly expressed pre-mRNA and contain the coding sequence for antibody polypeptide(s). The compositions of the invention include pre-trans-splicing molecules (PTMs) designed to interact with the target precursor messenger RNA molecule (target pre-mRNA) that is abundantly expressed or tumor specific and mediate a trans-splicing reaction resulting in the generation of novel chimeric RNA molecule (chimeric RNA) capable of encoding an antibody polypeptide. The invention provides for the in vivo production of chimeric RNA molecules that encode and result in the production of an antibody polypeptide that is therapeutically effective against, for example, infectious agents, cancer cells, transplantation antigens, rheumatoid arthritis, etc.

Abstract: Methods and compositions for generating novel nucleic acid molecules through targeted spliceosome mediated RNA trans-splicing that result in expression of a apoAI protein, an apoAI variant, the preferred embodiment referred to herein as the apoAI Milano variant, a pre-pro-apoAI or an analogue of apoAI. The methods and compositions include pre-trans-splicing molecules (PTMs) designed to interact with a target precursor messenger RNA molecule (target pre-mRNA) and mediate a trans-splicing reaction resulting in the generation of a novel chimeric RNA molecule (chimeric RNA) capable of encoding apoAI, the apoAI Milano variant, or an analogue of apoAI. The expression of this apoAI protein results in protection against vascular disorders resulting from plaque build up, i.e., atherosclerosis, strokes and heart attacks.

Abstract: The present invention provides methods and compositions for generating novel nucleic acid molecules through RNA trans-splicing that target a highly expressed pre-mRNA and contain the coding sequence for antibody polypeptide(s). The compositions of the invention include pre-trans-splicing molecules (PTMs) designed to interact with the target precursor messenger RNA molecule (target pre-mRNA) that is abundantly expressed or tumor specific and mediate a trans-splicing reaction resulting in the generation of novel chimeric RNA molecule (chimeric RNA) capable of encoding an antibody polypeptide. The invention provides for the in vivo production of chimeric RNA molecules that encode and result in the production of an antibody polypeptide that is therapeutically effective against, for example, infectious agents, cancer cells, transplantation antigens, rheumatoid arthritis, etc.

Abstract: The present invention provides methods and compositions for generating novel nucleic acid molecules through RNA trans-splicing that target a highly expressed pre-mRNA and contain the coding sequence of a protein or polypeptide of interest. The compositions of the invention include pre-trans-splicing molecules (PTMs) designed to interact with the target precursor messenger RNA molecule (target pre-mRNA) that is abundantly expressed, and mediate a trans-splicing reaction resulting in the generation of novel chimeric RNA molecule (chimeric RNA) capable of encoding a protein or polypeptide of interest. The invention provides for the in vivo production of chimeric RNA molecules that encode and result in the production of a protein or polypeptide of interest.

Abstract: The present invention provides, in certain aspects, a method of identifying a subject as having an increased risk of developing multiple sclerosis, comprising detecting in the subject the presence of a nucleotide variant in the interleukin 7 receptor alpha chain gene, whereby the presence of said variant identifies the subject as having an increased risk of developing multiple sclerosis.

Abstract: The molecules and methods of the present invention provide a means for in vivo production of a trans-spliced molecule in a selected subset of cells. The pre-trans-splicing molecules of the invention are substrates for a trans-splicing reaction between the pre-trans-splicing molecules and a pre-mRNA that is uniquely expressed in the specific target cells. The in vivo trans-splicing reaction provides a novel mRNA that is functional as mRNA or encodes a protein to be expressed in the target cells. The expression product of the mRNA is a protein of therapeutic value to the cell or host organism, a toxin that kills the specific cells or a novel protein not normally present in such cells. The invention further provides PTMs that have been genetically engineered for the identification of exon/intron boundaries of pre-mRNA molecules using an exon tagging method.