Hybrid nuclease molecules and methods for treating an immune-related disease or disorder in a mammal, and a pharmaceutical composition for treating an immune-related disease in a mammal.

Hybrid nuclease molecules and methods for treating an immune-related disease or disorder in a mammal, and a pharmaceutical composition for treating an immune-related disease in a mammal.

Some aspects of this disclosure provide compositions, methods, systems, and kits for controlling the activity and/or improving the specificity of RNA-programmable endonucleases, such as Cas9. For example, provided are guide RNAs (gRNAs) that are engineered to exist in an “on” or “off” state, which control the binding and hence cleavage activity of RNA-programmable endonucleases. Some aspects of this disclosure provide mRNA-sensing gRNAs that modulate the activity of RNA-programmable endonucleases based on the presence or absence of a target mRNA. Some aspects of this disclosure provide gRNAs that modulate the activity of an RNA-programmable endonuclease based on the presence or absence of an extended DNA (xDNA).

Some aspects of this disclosure provide compositions, methods, systems, and kits for controlling the activity and/or improving the specificity of RNA-programmable endonucleases, such as Cas9. For example, provided are guide RNAs (gRNAs) that are engineered to exist in an “on” or “off” state, which control the binding and hence cleavage activity of RNA-programmable endonucleases. Some aspects of this disclosure provide mRNA-sensing gRNAs that modulate the activity of RNA-programmable endonucleases based on the presence or absence of a target mRNA. Some aspects of this disclosure provide gRNAs that modulate the activity of an RNA-programmable endonuclease based on the presence or absence of an extended DNA (xDNA).

Embodiments of the present disclosure generally relate to methods and compositions for stabilizing biological material using intrinsically disordered proteins. In an embodiment, a composition is provided, the composition including a first component comprising at least one intrinsically disordered protein; and a second component comprising at least one biological material of interest, at least one biologically-derived material of interest, or both, the second component being free of the at least one intrinsically disordered protein. The methods and compositions include at least one intrinsically disordered protein that can be modified to prevent, or at least mitigate, polymerization thereof and the formation of gel-like matrices, thereby, e.g., improving the ability of the intrinsically disordered proteins to protect and stabilize sensitive biological materials.

Embodiments of the present disclosure generally relate to methods and compositions for stabilizing biological material using intrinsically disordered proteins. In an embodiment, a composition is provided, the composition including a first component comprising at least one intrinsically disordered protein; and a second component comprising at least one biological material of interest, at least one biologically-derived material of interest, or both, the second component being free of the at least one intrinsically disordered protein. The methods and compositions include at least one intrinsically disordered protein that can be modified to prevent, or at least mitigate, polymerization thereof and the formation of gel-like matrices, thereby, e.g., improving the ability of the intrinsically disordered proteins to protect and stabilize sensitive biological materials.

Methods and composition related to the engineering of a novel protein with methionine-γ-lyase enzyme activity are described. For example, in certain aspects there may be disclosed a modified cystathionine-γ-lyase (CGL) comprising one or more amino acid substitutions and capable of degrading methionine. Furthermore, certain aspects of the invention provide compositions and methods for the treatment of cancer with methionine depletion using the disclosed proteins or nucleic acids.

Methods and composition related to the engineering of a novel protein with methionine-γ-lyase enzyme activity are described. For example, in certain aspects there may be disclosed a modified cystathionine-γ-lyase (CGL) comprising one or more amino acid substitutions and capable of degrading methionine. Furthermore, certain aspects of the invention provide compositions and methods for the treatment of cancer with methionine depletion using the disclosed proteins or nucleic acids.

Genetically modified compositions, such as non-viral vectors and T cells, for treating cancer are disclosed. Also disclosed are the methods of making and using the genetically modified compositions in treating cancer.

Genetically modified compositions, such as non-viral vectors and T cells, for treating cancer are disclosed. Also disclosed are the methods of making and using the genetically modified compositions in treating cancer.