Nucleic acids and proteins having a mutant C-RAF sequence, and methods of identifying patients having cancer who are likely to benefit from a combination therapy and methods of treatment are provided.

Disclosed herein are compositions and methods for the expression of a gene of interest. The disclosed methods may employ codon-optimization and introduction of non-endogenous restriction sites for efficient expression of a gene. The methods may further employ introduction of a gene variant of interest, such that the disclosed methods, compositions, and systems may be used to determine the significance of a variant of interest. Further disclosed are compositions, systems, and methods for the characterization of gene variants, and other mutations that may impact the function of the protein of interest.

In some aspects, provided herein are computational methods for structure-based protein design. These new methods and incorporated algorithms speed-up computational structure-based protein design while maintaining accurate calculations, allowing for larger, previously infeasible protein designs. In another aspect, provided herein are mutant c-RAF proteins, and conjugates comprising the same. The conjugates may be used in methods of treating cancer in a subject, such as in methods of treating a KRas mutant cancer.

Compositions and methods for stimulating proliferation and/or migration of melanocytes in order to re-pigment skin regions, using ROCK inhibitors and optionally SIK inhibitors.

Genetically modified cells that are compatible with multiple subjects, e.g., universal donor cells, and methods of generating said genetic modified cells are provided herein. The universal donor cells comprise at least one genetic modification within or near a gene that encodes one or more MHC-I or MHC-II human leukocyte antigens or a component or a transcriptional regulator of a MHC-I or MHC-II complex, wherein genetic modification comprises an insertion of a polynucleotide encoding a tolerogenic factor and/or survival factor. The universal donor cells may further comprise at least one genetic modification within or near a gene that encodes a survival factor, wherein said genetic modification comprises an insertion of a polynucleotide encoding a second tolerogenic factor and/or a different survival factor.

Compositions and methods for treating melanoma are provided. Compositions include BRAF.sub.V600E-based peptides, alone or admixed with T helper peptides. Other compositions include nucleic acid sequences encoding the BRAF.sub.V600E-based peptides, alone or admixed with nucleic acid sequences T helper peptides. Dendritic cells pretreated with the BRAF.sub.V600E-based peptides, alone or admixed with T helper peptides, are also provided. These compositions are useful to treat melanoma, optionally co-administered with antibodies to checkpoint inhibitors or molecules that mimic the action of such antibodies.

A nucleic acid complex that exhibits an excellent antisense effect in the skeletal muscle and/or heart muscle, and a composition for treating or preventing a muscle disease that develops in the skeletal muscle, heart muscle, and the like having the nucleic acid complex as an active ingredient is disclosed. Also provided is a double-stranded nucleic acid complex in which a first nucleic acid strand that hybridizes to the transcription product of a target gene and has an antisense effect on the transcription product is annealed with a second nucleic acid strand that has a base sequence complementary to the first nucleic acid strand and is bound to cholesterol or analog thereof.

The disclosure provides compositions and methods useful for the depletion of a specific population of endogenous hematopoietic stem cells and/or immune cells from a subject prior to transplantation with genetically modified stem cells to improve the engraftment of the transplanted stem cells and provide gene therapy. The disclosure provides compositions and methods for the treatment of various hematopoietic diseases, metabolic disorders, cancers, and autoimmune diseases, among others. Described herein are antibodies, antigen-binding fragments, and conjugates thereof that can be applied to effect the treatment of these conditions, for instance, by depleting a population of CD117+ or CD45+ cells in a patient, such as a human.

Provided herein, among other things, is an engineered non-plant cell that produces a tropane alkaloid product, a precursor of a tropane alkaloid product, or a derivative of a tropane alkaloid product. A method for producing a tropane alkaloid, a precursor of a tropane alkaloid product, or a derivative of a tropane alkaloid product that makes use of the cell is also described.

The present invention relates to the field of cancer biology and immunology. More specifically, the present invention relates to the use of genetically modified immune cells in combination with certain chemotherapeutic agents for the treatment of cancer, wherein the genetically modified immune cells are resistant to said chemotherapeutic agents.