Abstract: The present invention provides compositions and methods for the treatment or prevention of a neurological disease or disorder of the central nervous system (e.g., a storage disorder, lysosomal storage disorder, neurodegenerative disease, etc.) by reconstitution of brain myeloid cell and microglia upon transplantation of hematopoietic cells enriched in microglia reconstitution potential. The invention also provides compositions and methods for ablating and reconstituting microglia.

Abstract: The disclosed invention provides a method of treating a central nervous system (CNS) disease or disorder comprising administering to a subject diagnosed with the CNS disease or disorder a composition comprising a population of genetically modified, programmed cell death-1 receptor ligand (PD-L1)+-expressing hematopoietic stem cells (HSCs), wherein the CNS disease or disorder involves inflammation of the CNS. In one embodiment, the CNS disease or disorder is Multiple Sclerosis (MS). In certain aspects, the hematopoietic stem cells (HSCs) are obtained from a subject having a CNS disease or disorder prior to modification.

Abstract: The invention relates to the field of gene therapy and more specifically to hematopoietic stem and progenitor cells that have been genetically modified to express functional progranulin. Suitably, HSPCs that have gene edited using CRISPR/Cas technology, or have been transduced with lentiviral gene delivery vehicles. The invention also relates to the use of such modified HSPCs in therapy. In particular, the invention relates to use of the modified progranulin expressing HSPCs in the prevention or treatment of a neurodegenerative disease mediated by dysfunctional progranulin expression, such as frontotemporal dementia (FTD).

Abstract: The present invention provides compositions and methods for the treatment or prevention of a lysosomal disease or disorder involving increasing the level, expression, or activity of a metallothionein polypeptide or polynucleotide in the subject.

Abstract: The present disclosure features methods and compositions for treating Alzheimer's disease. The disclosed methods comprise administering to a subject having or suspected of having Alzheimer's a hematopoietic stem progenitor cell expressing at least one neuroprotective agent, such as ApoE2, Trem2, and/or a metallothionein.

Abstract: The present disclosure features methods and compositions for expressing transgenes in microglia. The disclosed compositions comprise isolated fragments of human and murine translocator protein (TSPO) promoters and expression cassettes comprising the same. The methods involve using these promoters and/or expression cassettes to express transgenes in a cell.

Abstract: A gene vector for use in gene therapy comprising at least one miRNA sequence target operably linked to a nucleotide sequence having a corresponding miRNA in a hematopoietic progenitor cell (HSPC) or hematopoietic stem cell (HSC) which prevents or reduces expression of the nucleotide sequence in a HSPC or HSC but not in a differentiated cell.

Abstract: The present disclosure features CX3CR1 hemizygous and/or homozygous defective cells and methods of using such cells for the treatment of a metabolic or neurological disorder. The disclosed methods include methods for making and modifying CX3CR1 hemizygous and/or homozygous defective cells, such as hematopoietic stem progenitor cells. Other disclosed methods include methods of treating a subject having or suspected of having a metabolic or neurological disease comprising administering to the subject a composition comprising a hemizygous and/or homozygous defective CX3CR1 cell. The CX3CR1 hemizygous and/or homozygous defective cell may be modified to have a nucleic acid molecule encoding a therapeutic polypeptide or polynucleotide.

Abstract: The present disclosure features methods and compositions for treating amyotrophic lateral sclerosis (ALS). The disclosed methods comprise administering to a subject having or suspected of having ALS a hematopoietic stem progenitor cell expressing at least one neuroprotective agent. The compositions disclosed comprise hematopoietic stem progenitor cells transduced to express a neuroprotective agent.

Abstract: A gene vector for use in gene therapy comprising at least one miRNA sequence target operably linked to a nucleotide sequence having a corresponding miRNA in a hematopoietic progenitor cell (HSPC) or hematopoietic stem cell (HSC) which prevents or reduces expression of the nucleotide sequence in a HSPC or HSC but not in a differentiated cell.

Abstract: The present invention provides compositions and methods for targeting cells for therapeutic and/or diagnostic purposes, e.g., delivery of therapeutic and/or diagnostic agents to a cell. Nanoparticles and polymers functionalized with capture molecules, reporter molecules, and/or therapeutic agents are provided for the treatment or prevention of disease, including neurological diseases associated with neuroinflammation, and cancer.

Abstract: The invention features compositions and methods for the treatment and prevention of peroxisomal diseases (e.g., neonatal adrenoleukodystrophy and Zellweger syndrome), including in a subject selected as having increased levels of metallothionein polypeptides. The invention also provides compositions and methods for identifying a subject having a peroxisomal disease involving detecting metallothionein polypeptides or polynucleotdies.

Abstract: The present invention provides compositions and methods for the treatment or prevention of a neurological disease or disorder of the central nervous system (e.g., a storage disorder, lysosomal storage disorder, neurodegenerative disease, etc.) by reconstitution of brain myeloid cell and microglia upon transplantation of hematopoietic cells enriched in microglia reconstitution potential. The invention also provides compositions and methods for ablating and reconstituting microglia.

Abstract: The present invention provides compositions and methods for the treatment or prevention of a lysosomal disease or disorder involving increasing the level, expression, or activity of a metallothionein polypeptide or polynucleotide in the subject.

Abstract: A gene vector for use in gene therapy comprising at least one miRNA sequence target operably linked to a nucleotide sequence having a corresponding miRNA in a hematopoietic progenitor cell (HSPC) or hematopoietic stem cell (HSC) which prevents or reduces expression of the nucleotide sequence in a HSPC or HSC but not in a differentiated cell.

Abstract: A gene vector for use in gene therapy comprising at least one miRNA sequence target operably linked to a nucleotide sequence having a corresponding miRNA in a hematopoietic progenitor cell (HSPC) or hematopoietic stem cell (HSC) which prevents or reduces expression of the nucleotide sequence in a HSPC or HSC but not in a differentiated cell.

Abstract: A gene vector for use in gene therapy comprising at least one miRNA sequence target operably linked to a nucleotide sequence having a corresponding miRNA in a hematopoietic progenitor cell (HSPC) or hematopoietic stem cell (HSC) which prevents or reduces expression of the nucleotide sequence in a HSPC or HSC but not in a differentiated cell.

Abstract: The invention relates to compositions for the cryopreservation of transduced haematopoietic cells, in particular transduced haematopoietic stem cells. The invention also relates to methods of preserving the viability of transduced haematopoietic cells using said compositions.

Abstract: A gene vector for use in gene therapy comprising at least one miRNA sequence target operably linked to a nucleotide sequence having a corresponding miRNA in a hematopoietic progenitor cell (HSPC) or hematopoietic stem cell (HSC) which prevents or reduces expression of the nucleotide sequence in a HSPC or HSC but not in a differentiated cell.

Abstract: A gene vector for use in gene therapy comprising at least one miRNA sequence target operably linked to a nucleotide sequence having a corresponding miRNA in a hematopoietic progenitor cell (HSPC) or hematopoietic stem cell (HSC) which prevents or reduces expression of the nucleotide sequence in a HSPC or HSC but not in a differentiated cell.