Provided herein are methods of treating cancer comprising administering a PARP inhibitor which may be combined with a BRD4 inhibitor. In one embodiment, the present disclosure provides a method for treating cancer in a subject comprising administering an effective amount of a poly-ADP-ribose polymerase (PARP) inhibitor in combination with a bromodomain-containing protein 4 (BRD4) inhibitor to the subject. In some aspects, the administration of the PARP inhibitor and BRD4 inhibitor results in greater reduction in tumor growth or greater reduction in tumor mass relative to administration of PARP inhibitor or BRD4 inhibitor alone.

Disclosed herein are compositions and methods of treating disclosure provides for compounds for use in treating Mitochondrial Neurogastrointestinal Encephalopathy Syndrome (MNGIE). In some embodiments, the compounds have cell penetrating activity and thymidine phosphorylase activity. In certain embodiments, the compounds disclosed herein comprise: a) at least one cell-penetrating peptide (CPP) moiety; and b) a thymidine phosphorylase, or an active fragment or analog thereof (TP), wherein the CPP is coupled, directly or indirectly, to TP.

The invention provides methods and compositions for improved production of large quantities of unencapsidated doublestrand RNA (dsRNA) in vivo. The disclosed methods and compositions, comprising co-expression of genes encoding orotate phospori-bosyl transferase, bacteriophage coat protein and dsRNA produce a significant improvement over current in vivo methods of producing unencapsidated dsRNA.

The present disclosure relates to isolated non-naturally occurring delivery constructs comprising a bacterial toxin-derived delivery construct coupled to a biologically active therapeutic cargo; wherein the delivery construct is capable of delivering the biologically active cargo via transcytosis transport across an epithelial cell; and wherein the delivery construct does not comprise a bacterial toxin-derived translocation domain or a bacterial toxin-derived catalytic (cytotoxic) domain.

The present invention provides, among other things, improved therapeutic compositions comprising a C3 fusion protein and methods of making and using the same. In particular, the present invention provides improved methods for the treatment of spinal cord injury and other CNS trauma and/or facilitate axon growth or other tissue repair.

Compositions and methods comprising polynucleotides and polypeptides having glyphosate-N-acetyltransferase (GLYAT) activity are provided. In specific embodiments, the sequence has an improved property, such as, but not limited to, an improved specificity for glyphosate when compared to an appropriate control resulting in decreased off target acetylation of, e.g. an amino acid such as aspartate. Further provided are nucleic acid constructs, plants, plant cells, explants, seeds and grain having the GLYAT sequences. Various methods of employing the GLYAT sequences are provided. Such methods include methods for producing a glyphosate tolerant plant, plant cell, explant or seed and methods of controlling weeds in a field containing a crop employing the plants and/or seeds disclosed herein.

Described herein are methods for transfecting mesenchymal stem cells (MSCs) with a nucleic acid construct using a cationic polymer, a first reagent capable of redirecting endocytosed nucleic acids from intracellular acidic compartments, and a second agent capable of stabilizing a microtubular network of the MSCs. The methods are free of virus-based transfection vehicle materials and the transfected MSCs have substantially unchanged multipotent phenotype. In certain embodiments, the transfected MSCs express functional genes comprising suicide gene, such as cytosine deaminase or uracil phosphoribosyltransferase. Also described are methods for the treatment of diseases, such as cancer, using such transfected cells in combination with 5FC, 5FU, GCV, as well as kits and composition relating thereof.

The invention relates to a method for producing aminobenzoic acid or an aminobenzoic acid derivative using a fermentation process, in which (I) the aminobenzoic acid formed in the fermentation broth obtained by the fermentation is bound in part, or as much as possible based on the solubility equilibrium, as insoluble calcium-aminobenzoate, said insoluble calcium-aminobenzoate is then (II) either isolated as such or in a mixture with the microorganism used in the fermentation and transitioned into a water soluble form, while separating an insoluble calcium salt which is different from the calcium-aminobenzoate, and then (III) by introducing carbon dioxide under pressure into the aqueous solution from the precipitated calcium salt has been released, aminobenzoic acid is precipitated.

IL-2 fusion toxins, e.g., bivalent-IL2 fusion toxins, and methods of use thereof.

The present disclosure relates to pharmaceutical compositions comprising a non-naturally occurring fusion molecule and one or more pharmaceutically acceptable carriers, formulated for oral delivery to a subject, and designed to provide for improved, effective therapies for treatment of, e.g., inflammatory diseases, autoimmune diseases, cancer, metabolic disorders, and growth deficiency disorders. The present disclosure relates to a non-toxic mutant form of the Vibrio cholera Cholix gene (ntCholix), a variant of Cholix truncated at amino acid A.sup.386 (Cholix.sup.386) and the use of other various Cholix-derived polypeptide sequences to enhance intestinal delivery of biologically-active therapeutics. The systems and methods described herein provide for: the ability to deliver macromolecule doses without injections; the ability to deliver cargo such as siRNA or antisense molecules into intracellular compartments where their activity is required; and the delivery of nanoparticles and dendrimer-based carriers across biological membranes.