Embodiments of the disclosure relate to modulation of an immune response comprising modulating the interaction between a death associated protein kinase (DAPK) and stimulator of interferon genes protein (STING) pathway. In certain embodiments, a method is provided for treating a subject for an inflammatory or autoimmune disease, or cancer, or a side effect or symptom thereof by administering an agent that modulates the interaction between a DAPK and the STING pathway.

Described herein are methods and vectors for rational, multiplexed manipulation of chromosomes within open reading frames (e.g., in protein libraries) or any segment of a chromosome in a cell or population of cells, in which various CRISPR systems are used.

Embodiments disclosed herein provide methods, including computer-implemented methods, for designing guide sequence which may be incorporated into custom, large scale guide sequence libraries. The methods require only a list of target genes as input and utilize on target and off target scores to generate an optimal set of guide sequences for a set of target genes. In certain embodiments, the methods may also utilize multi-tissue RNA-sequencing data and/or protein annotation to design targets to genes that are highly expressed and/or contain a functional protein domain. The invention further comprises guide libraries, cells comprising said guide libraries. Computer-implemented embodiments further improve computer system function by reducing excessive user wait time through the use of data structures that reduce search from linear to logarithmic time.

The present invention relates to screening methods for identifying suppressors or activators of a pathway.

Provided herein are methods and compositions to make guide nucleic acids (gNAs), nucleic acids encoding gNAs, collections of gNAs, and nucleic acids encoding for a collection of gNAs from any source nucleic acid. Also provided herein are methods and compositions to use the resulting gNAs, nucleic acids encoding gNAs, collections of gNAs, and nucleic acids encoding for a collection of gNAs in a variety of applications.

Described herein are methods and vectors for rational, multiplexed manipulation of chromosomes within open reading frames (e.g., in protein libraries) or any segment of a chromosome in a cell or population of cells, in which various CRISPR systems are used.

Described herein are methods and vectors for rational, multiplexed manipulation of chromosomes within open reading frames (e.g., in protein libraries) or any segment of a chromosome in a cell or population of cells, in which various CRISPR systems are used.

Described herein are methods and vectors for rational, multiplexed manipulation of chromosomes within open reading frames (e.g., in protein libraries) or any segment of a chromosome in a cell or population of cells, in which various CRISPR systems are used.

The present invention provides methods for introducing mutations to primary cells and selecting for the mutations to obtain a population of cells for modeling cancer. Such methods may comprise at least one round of introducing one or more mutations into one or more cells in a population of cells in vitro and culturing the cells until the mutation(s) are positively selected in the population. The cells may be cultured in vitro. The cells may be cultured in vivo. In certain embodiments, the cells are positively selected in vivo in order to select for cells capable of evading the immune system. In certain embodiments, cells are selected in an immune competent animal model. The cells may primary cells. The population of cells may be used for drug screening and for studying cancer.

A suppressor or inhibitor of expression and/or function of 4 a gene, a kinase or ubiquitin ligase, for use in the treatment of a protein conformational disorder is provided.