Abstract: Methods and compositions for genetically modifying a cell are provided.

Abstract: The disclosure provides lipid nanoparticle (LNP) compositions of ionizable lipids, helper lipids, neutral lipids, and PEG lipids useful for the delivery of biologically active agents, for example delivering biologically active agents to cells to prepare engineered cells. The LNP compositions disclosed herein are useful in methods of gene editing and methods of delivering a biologically active agent and methods of modifying or cleaving DNA.

Abstract: The present disclosure relates to inhibitors of DNA protein kinase, and compositions and methods of use thereof. In some embodiments, the inhibitors have the structure of Formula I: or a salt thereof, wherein: x1 is C—R3 or N; R1 is C1-C3 alkyl; R2 is cycloalkyl or heterocyclyl, and cycloalkyl and heterocyclyl are optionally substituted with one or more R6; R3 is H or C1-C3 alkyl; R4 is H or C1-C3 alkyl; R5 is C1-C3 alkyl; each R6 is independently selected from hydroxy, halo, alkyl, alkoxy, cycloalkyl, amino, and cyano, or two R6, taken together with the atom or atoms to which they are bonded, form a spirocyclic or fused ring; and R7 is H or C1-C3 alkyl.

Abstract: The disclosure provides lipid nanoparticle (LNP) compositions of ionizable lipids, helper lipids, neutral lipids, and PEG lipids useful for the delivery of biologically active agents, for example delivering biologically active agents to cells to prepare engineered cells. The LNP compositions disclosed herein are useful in methods of gene editing and methods of delivering a biologically active agent and methods of modifying or cleaving DNA.

Abstract: Described herein is a bispecific scFv construct agonizing both CD3 and CD28 pathways. Typically, the construct is soluble and activates, expands, and differentiates human T cells ex vivo. Related compositions and methods are also described, such as methods for expanding, activating, and or differentiating T cells ex vivo and methods of treating cancer.

Abstract: Compositions and methods for multiplex delivery and gene editing in vitro are provided.

Abstract: Provided herein are engineered nucleic acids, engineered mRNAs, engineered polypeptides, and engineered pentamerized polypeptides, human and murine, each of which include sequences of VISTA, ICOS-L, PD-L1 or B7-H4 extracellular domains operably linked to the pentamerization domain of COMP. A soluble form of the pentamerized polypeptides has T-cell inhibitory activity, in the case of VISTA, PD-L1 or B7H4, or T-cell stimulatory activity, in the case of ICOS-L. Methods of using same for treatment of a subject in need of T-cell modulating activity are provided.

Abstract: Provided herein are engineered nucleic acids, engineered mRNAs, engineered polypeptides, and engineered pentamerized polypeptides, human and murine, each of which include sequences of VISTA, ICOS-L, PD-L1 or B7-H4 extracellular domains GO operably linked to the pentamerization domain of COMP. A soluble form of the pentamerized polypeptides has T-cell inhibitory activity, in the case of VISTA, PD-L1 or B7H4, or T-cell stimulatory activity, in the case of ICOS-L. Methods of using same for treatment of a subject in need of T-cell modulating activity are provided.

Abstract: Disclosed are short DNA aptamers that selectively recognize CD200R1, a protein expressed on the surface of myeloid and lymphoid cells that delivers immune inhibitory signals to modulate inflammation when engaged with its ligand, CD200. Also disclosed is the use of said aptamers as therapeutic agents, for the purpose of decreasing inflammatory response; treatment of spinal cord injury; treatment of an immune related disease such as arthritis, asthma, allergy, infection; as a course of treatment during or after transplantation; or for treatment of an autoimmune disorder such as systemic lupus erythematosus, Parkinson's Disease, or multiple sclerosis.

Abstract: Disclosed are short DNA aptamers that selectively recognize CD200R1, a protein expressed on the surface of myeloid and lymphoid cells that delivers immune inhibitory signals to modulate inflammation when engaged with its ligand, CD200. Also disclosed is the use of said aptamers as therapeutic agents, for the purpose of decreasing inflammatory response; treatment of spinal cord injury; treatment of an immune related disease such as arthritis, asthma, allergy, infection; as a course of treatment during or after transplantation; or for treatment of an autoimmune disorder such as systemic lupus erythematosus, Parkinson's Disease, or multiple sclerosis.

Abstract: Disclosed are short DNA aptamers that selectively recognize CD200R1, a protein expressed on the surface of myeloid and lymphoid cells that delivers immune inhibitory signals to modulate inflammation when engaged with its ligand, CD200. Also disclosed is the use of said aptamers as therapeutic agents, for the purpose of decreasing inflammatory response; treatment of spinal cord injury; treatment of an immune related disease such as arthritis, allergy, infection; as a course of treatment during or after transplantation; or for treatment of an autoimmune disorders such as systemic lupus erythematosus, Parkinson's Disease, or multiple sclerosis.

Abstract: Disclosed are short DNA aptamers that selectively recognize CD200R1, a protein expressed on the surface of myeloid and lymphoid cells that delivers immune inhibitory signals to modulate inflammation when engaged with its ligand, CD200. Also disclosed is the use of said aptamers as therapeutic agents, for the purpose of decreasing inflammatory response; treatment of spinal cord injury; treatment of an immune related disease such as arthritis, allergy, infection; as a course of treatment during or after transplantation; or for treatment of an autoimmune disorders such as systemic lupus erythematosus, Parkinson's Disease, or multiple sclerosis.