Methods and compositions including granulin/epithelin modules (GEMs) or combinations thereof suitable for treating neurodegenerative diseases. Also disclosed are methods of treatment of neurodegenerative diseases, such as methods of administering therapeutic recombinant GEM proteins or gene therapies for delivering recombinant GEM gene products.

Aspects of the present disclosure relate to methods and compositions related to related to the preparation of immune cells, including engineered T cells having T cell receptors that target human prostatic acid phosphatase (PAP) and are useful in prostate cancer therapy.

The disclosure provides a method for modulating gene expression in a cell-specific manner in response to an intracellular or extracellular stimulus. The disclosure provides a platform entitled the PROTEGE platform, which comprises a DNA binding module and a transcription factor binding module, referred to herein as PGM. The PGM binds the promoter region of a target gene with sequence specificity through the DNA binding module and also binds a TF through the TF-binding module. When the TF is activated in response to an intracellular or extracellular stimulus, it binds the PGM and, due to its close proximity to the promoter of the gene, modulates expression of a target gene in response to the stimulus.

Provided herein are engineered nucleic acids (e.g., expression vectors, including viral vectors, such as lentiviral vectors, adenoviral vectors, AAV vectors, herpes viral vectors, and retroviral vectors) that encode OCT4; KLF4; SOX2; or any combination thereof that are useful, for example, in inducing cellular reprogramming, tissue repair, tissue regeneration, organ regeneration, reversing aging, or any combination thereof in the central nervous system or ex vivo. Also provided herein are recombinant viruses (e.g., lentiviruses, alphaviruses, vaccinia viruses, adenoviruses, herpes viruses, retroviruses, or AAVs) comprising the engineered nucleic acids (e.g., engineered nucleic acids), engineered cells, compositions comprising the engineered nucleic acids, the recombinant viruses, engineered cells, engineered proteins, chemical agents that are capable of activating expression of OCT4; KLF4; SOX2; or any combination thereof, an engineered protein selected from the group consisting of OCT4; KLF4; SOX2; or any combination thereof, an antibody capable of activating expression of OCT4; KLF4; SOX2; or any combination thereof, and methods of treating a disease (e.g., a neurological disease), preventing a disease (e.g., neurological disease), regulating (e.g., inducing or inducing and then stopping) cellular reprogramming, regulating tissue repair, regulating tissue regeneration, or any combination thereof.

The invention provides improved gene therapy methods and compositions.

Provided herein are methods for inducing an immune response against an antigen in a subject. In some embodiments, the methods comprise administering a therapeutically effective amount of a vaccine and an interleukin 10 (IL-10) inhibitor to the subject. In some embodiments, the vaccine is an IL-10-deficient vaccine.