RNA molecules comprising a guide sequence portion having 17-50 contiguous nucleotides containing nucleotides in the sequence set forth in any one of SEQ ID NOs: 1-1538 and compositions, methods, and uses thereof.

The invention covers the use of certain classes of lipids including cationic lipids in ex-vivo dendritic cell therapies. The cationic lipids enhance antigen uptake, processing and presentation of the processed antigens by dendritic cells to CD8+and CD4+T-cells via the MHC classes I and II presentation pathways respectively. Antigen uptake via cationic lipid by dendritic cells result in significant lowering of the population of the immune suppressive regulatory T cells in the tumors and a significant increase of the tumor targeting cytotoxic T-cells. Loss of regulatory T cells and increase of tumor specific cytotoxic cells are conducive to effective elimination of the tumors.

Genetically modified CCNT1 and XPO1 genes encoding proteins that inhibit virus infection in cells. The genetically modified CCNT1 gene encodes a protein with a C261Y substitution with respect to the human CCNT1 protein. The genetically modified XPO1 gene encodes a protein with P411T, M412V, and/or F414S substitutions with respect to the human XPO1 protein. The genetically modified CCNT1 and XPO1 genes can be introduced in cells. The cells comprising the genetically modified CCNT1 and XPO1 genes can be introduced in a subject with a virus infection to treat the infection.

Provided herein are compositions, such as, for example, CXCL 10-secreting antigen presenting cells, and methods for ultrasound-induced blood-brain bander disruption (e.g., low-intensity pulsed ultrasound (LIPU)) to treat a brain cancer in a mammalian subject.

Methods of use of early apoptotic cell populations and compositions thereof disclosed herein, including methods of treating a cancer or a tumor, extending survival times of a subject suffering from a cancer or a tumor, and reducing the size or reducing the growth rate of a cancer or a tumor, wherein subjects are administered apoptotic cells or compositions thereof. Cancers may include solid tumors or diffuse cancers, for example leukemia. In certain instances compositions may include additional chemotherapeutic agent. Further, inactivated early apoptotic cell populations are disclosed and methods of making the same.

The present invention relates to an isolated cellular targeted delivery system comprising a CD45+ leukocyte cell comprising within said cell a complex of one or more iron binding proteins and an active pharmaceutically active substance and/or label as well as methods for producing such isolated cellular targeted delivery system and uses of such system for prophylaxis, therapy, diagnosis or theragnosis, in particular for prophylactic or therapeutic vaccination, therapy of cancer, particularly metastatic cancer or inflammatory diseases.

Compositions and methods for therapeutic use of engineered myeloid cells are described. Methods for increasing therapeutic effectiveness of immune cells by use of an immune cell inhibitory agent prior to therapy is described. Effective use of myeloid cells in combination therapy is described.

The present invention describes a method of treating, preventing, reducing the likelihood of or alleviating a symptom of Alzheimer's disease and associated conditions by increasing OPN expression. The invention further provides for a method of improving cognitive function in a subject in need thereof.

Described herein are chimeric receptors. Chimeric receptors comprise a cytoplasmic domain; a transmembrane domain; and an extracellular domain. In embodiments, the cytoplasmic domain comprises a cytoplasmic portion of a receptor that when activated polarizes a macrophage. In further embodiments, a wild-type protein comprising the cytoplasmic portion does not comprise the extracellular domain of the chimeric receptor. In embodiments, the binding of a ligand to the extracellular domain of the chimeric receptor activates the intracellular portion of the chimeric receptor. Activation of the intracellular portion of the chimeric receptor may polarize the macrophage into an M1 or M2 macrophage.

The present invention comprises a method of downregulating intracellular defenses by administering (5Z)-7-Oxozeaenol. This allows for improved delivery of RNA based gene vectors to natural killer, stem and macrophage cells. The resulting cells can be used in adoptive cell transfer therapies. Also provided are methods of treating virally induced inflammation via administration of (5Z)-7-Oxozeaenol together with an anti viral therapeutic.