Abstract: The present disclosure relates to compositions of matter and methods used to activate effector nucleic acids and effector targets in vivo via a CRISPR-based cascade system. The compositions and methods achieve non-specific delivery of cascade system components to cells yet the cascade system works in a cell-specific manner.

Abstract: Described herein are compositions and methods for treating a subject having or at risk of developing a neurocognitive disorder, such as Alzheimer's disease or Nasu-Hakola disease. For example, using the compositions and methods of the disclosure, a subject having or at risk of developing a neurocognitive disorder may be administered one or more cells that contain a transgene encoding triggering receptor expressed on myeloid cells two (TREM2), such as a population of CD34+ hematopoietic stem or progenitor cells that express TREM2, thereby treating or preventing the disorder.

Abstract: Described herein are compositions and methods for treating a subject having or at risk of developing a neurocognitive disorder, such as Alzheimer's disease or Nasu-Hakola disease. For example, using the compositions and methods of the disclosure, a subject having or at risk of developing a neurocognitive disorder may be administered one or more cells that contain a transgene encoding triggering receptor expressed on myeloid cells two (TREM2), such as a population of CD34+ hematopoietic stem or progenitor cells that express TREM2, thereby treating or preventing the disorder.

Abstract: Described herein are compositions and methods for treating a patient having or at risk of developing a neurocognitive disorder, such as Alzheimer's disease, Parkinson's disease, and/or a frontotemporal lobar dementia. Using the compositions and methods of the disclosure, a patient, such as an adult human patient, may be provided one or more agents that elevate the expression and/or activity levels of a protein or series of proteins whose deficiency is associated with the corresponding disease. Exemplary agents that may be used in conjunction with the compositions and methods of the disclosure for this purpose include cells, such as cells, that contain nucleic acids encoding the protein or proteins of interest, as well as vectors, such as viral vectors, encoding the protein or proteins of interest. Additional examples of such agents include the protein or proteins themselves, as well as interfering RNA molecules that stimulate their endogenous expression.

Abstract: Described herein are methods for treating a subject having or at risk of developing a neurocognitive disorder, such as frontotemporal lobar degeneration or neuronal ceroid lipofuscinosis, by administering cells that contain a transgene encoding a progranulin (PGRN) or a granulin (GRN) or cells that express the PGRN or the GRN to the subject. Also disclosed are compositions comprising cells containing the transgene encoding the PGRN or the GRN.