Disclosed are compounds that possess inhibitory activity against FAK. Also disclosed are pharmaceutical compositions containing the compounds and methods of using the compounds to treat cancer mediated by aberrant FAK activity.

The present disclosure provides compositions and methods for the prevention or treatment of ocular neovascularization, such as AMD, in a human subject, by administering subretinally a pharmaceutical composition comprising a pharmaceutically effective amount of a vector comprising a nucleic acid encoding soluble Fms-related tyrosine kinase-1 (sFlt-1) protein to the human subject.

The present disclosure provides improved genome editing compositions and methods for editing a human BTK gene. The disclosure further provides genome edited cells for the prevention, treatment, or amelioration of at least one symptom of X-linked agammaglobulinemia (XLA).

Provided herein are compositions comprising a RIPK2 inhibitor and methods of using the RIPK2 inhibitor for treating or preventing neurodegenerative diseases or disorders. Also provided herein are methods of screening or identifying therapeutic agents useful for treating or preventing neurodegenerative diseases or disorders.

Chimeric receptors featuring major histocompatibility molecules grafted onto T cell receptor molecules and surrogate co-receptors featuring cell surface receptor ligands fused with signaling molecule domains. The chimeric receptors can be used to redirect cells, altering their specificity. T cells expressing chimeric receptors may bind to TCRs of target T cells for which their chimeric receptors are specific. Surrogate co-receptors may be used to help enhance TCR-CD3 signaling as part of this modular receptor system. The chimeric receptors and surrogate coreceptors may be used to help eliminate autoreactive T cells or program T cells to desired effector functions.

The disclosure relates to a recombinant membrane span protein complex, comprising (1) a fusion protein, comprising a membrane span protein fused to a kinase domain, preferably a constitutive kinase and (2) a reporter construct comprising a polypeptide, interacting with the membrane span protein, fused to a reporter phosphorylation domain. The disclosure relates further to the uses of such membrane span protein complex for the detection of compounds that interact with the membrane span protein and for the screening and/or detection of inhibitors of the compound-membrane span protein interactions. In a preferred embodiment, the membrane span protein is a G protein coupled receptor (GPCR) and the method is used for the screening and/or detection of inhibitors of the ligand-receptor binding.

In one aspect of the present disclosure is a method of harvesting viral titer about every 40 hours to about every 56 hours following induction of stable producer cell line cells, wherein the viral titer is at least partially harvested in a serum-free medium. In another aspect of the present disclosure is a method of harvesting vector supernatant comprising: generating stable producer cell line cells; inducing viral vector production from the generated stable producer cell line cells; and repeatedly harvesting the viral vectors from the induced generated stable producer cell line cells in serum-free media every about 40 to about 56 hours following an initial harvesting of the viral vectors.

The present disclosure provides improved genome editing compositions and methods for editing a human BTK gene. The disclosure further provides genome edited cells for the prevention, treatment, or amelioration of at least one symptom of X-linked agammaglobulinemia (XLA).

Provided are vaccines, polypeptides and polynucleotides based on mutant CALR and JAK2 sequences, vectors, host cells, viruses, and methods of making and using them. The disclosure also provides methods of inducing an immune response and methods of treating, preventing, reducing a risk of onset or delaying the onset of a clinical condition characterized by an expression of JAK2V617F or CALR exon 9 mutant, or both JAK2V617F and CALR exon 9 mutant, wherein the method comprises a plurality of administrations of any of the compositions comprising polynucleotides, polypeptides or vectors disclosed herein.

The invention disclosed herein is based on the identification of novel mutations in the JAK2 gene and JAK2 protein. The invention provides compositions and methods useful for diagnosing hematopoietic diseases including, for example, myeloproliferative diseases. The invention also provides compositions and methods useful for determining a prognosis of an individual diagnosed as having a hematopoietic disease.