The present technology is directed to methods of treatment utilizing inhibitors of HuR interaction with RNA, where the inhibitors are of Formula I where R.sup.1 is; and X.sup.1 is OH, NH—OH, or 0-(C.sub.1-C.sub.8 unsubstituted alkyl).

##STR00001##

The present technology is directed to methods of treatment utilizing inhibitors of HuR interaction with RNA, where the inhibitors are of Formula I where R.sup.1 is; and X.sup.1 is OH, NH—OH, or 0-(C.sub.1-C.sub.8 unsubstituted alkyl).

##STR00001##

The present invention provides a process for the recovery and/or purification of a recombinantly expressed intracellular protein comprising the sequence of Annexin A5 (AnxA5) from an endotoxin-producing host cell with a cell wall, wherein the process comprises releasing the intracellular protein from the host cell, characterised in that the step of releasing the intracellular AnxA5 protein is conducted in the presence of a homogenisation buffer comprising non-ionic detergent, and preferably wherein the process does not include any centrifugation steps for the recovery and/or purification of the AnxA5 protein after its release from the host cell and/or in which the AnxA5 protein remains in solution throughout the process except when temporarily bound to any chromatographic resins.

Genetically modified cells that are compatible with multiple subjects, e.g., universal donor cells, and methods of generating said genetic modified cells are provided herein. The universal donor cells comprise at least one genetic modification within or near a gene that encodes one or more MHC-I or MHC-II human leukocyte antigens or a component or a transcriptional regulator of a MHC-I or MHC-II complex, wherein genetic modification comprises an insertion of a polynucleotide encoding a tolerogenic factor and/or survival factor. The universal donor cells may further comprise at least one genetic modification within or near a gene that encodes a survival factor, wherein said genetic modification comprises an insertion of a polynucleotide encoding a second tolerogenic factor and/or a different survival factor.

Genetically modified cells that are compatible with multiple subjects, e.g., universal donor cells, and methods of generating said genetic modified cells are provided herein. The universal donor cells comprise at least one genetic modification within or near a gene that encodes one or more MHC-I or MHC-II human leukocyte antigens or a component or a transcriptional regulator of a MHC-I or MHC-II complex, wherein genetic modification comprises an insertion of a polynucleotide encoding a tolerogenic factor and/or survival factor. The universal donor cells may further comprise at least one genetic modification within or near a gene that encodes a survival factor, wherein said genetic modification comprises an insertion of a polynucleotide encoding a second tolerogenic factor and/or a different survival factor.

Methods and compositions for delivering a payload at TnMUC1 positive cancer cells. Anti-TnMUC1 CARs and transgene payloads can be engineered into immune cells so that the transgene payload is expressed and delivered at desired times from the immune cell. Such anti-TnMUC1 CAR T-cells with transgene payloads can be combined with the administration of other molecules, e.g., other therapeutics such as anticancer therapies.

Methods and compositions for delivering a payload at TnMUC1 positive cancer cells. Anti-TnMUC1 CARs and transgene payloads can be engineered into immune cells so that the transgene payload is expressed and delivered at desired times from the immune cell. Such anti-TnMUC1 CAR T-cells with transgene payloads can be combined with the administration of other molecules, e.g., other therapeutics such as anticancer therapies.

The instant application relates to deazapurines, thienopyrimidines and furopyrimidines with zinc-binding moiety based derivatives and their use in the treatment of phosphoinositide 3-kinase related diseases and disorders such as cancer. The instant application further relates to the the treatment of histone deacetylase related disorders and diseases related to both histone deacetylase and phosphoinositide 3-kinase.

The present disclosure provides binding proteins, such as antibodies and binding fragments thereof, that bind beta klotho, including human beta klotho, and methods of their use, including in the treatment of nonalcoholic steatohepatitis. The present disclosure also provides exemplary specific sequences of complementarity determining regions, variable regions, heavy chains, and light chains of the antibodies and/or binding fragments thereof.

The present invention relates to compounds useful of inhibitors of protein kinases. The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of various disease, conditions, or disorders.