Provided are methods for modification of amino acid sequence and increasing levels of expression of ApoA-I Binding Protein to treat: a neuropathic pain, a CNS inflammation, an allodynia, a post nerve injury pain, a post-surgical pain, a chemotherapeutic-induced peripheral neuropathy, a neurodegeneration, including for example, a neurodegenerative disease or condition such as Alzheimer's disease, a hyperalgesia, primary headaches such as migraines and cluster headaches, glaucoma or other inflammatory diseases of the eye, lung inflammation, asthma, HIV infection, vascular inflammation, atherosclerosis and cardiovascular disease. Provided are methods comprising administering pharmaceutical compositions comprising a recombinantly modified APOA1BP polypeptide to treat a neuropathic pain, an allodynia, a hyperalgesia, a neurodegenerative disease, a primary headache such as a migraine, glaucoma, lung inflammation and asthma, acute respiratory distress syndrome (ARDS), sepsis, viral infection, including influenza, coronavirus (for example, COVID-19) or HIV infection, or its comorbidities, and/or vascular inflammation, atherosclerosis and cardiovascular disease.

The present disclosure provides compositions and methods for the genetic modification of cells, including, but not limited to, hepatocytes. The compositions and methods can comprise lipid nanoparticles, wherein the lipid nanoparticles comprise at least one bioreducible ionizable cationic lipid, at least one structural lipid, at least one phospholipid and at least one PEGylated lipid.

The present invention concerns the use of peptidyl-prolyl isomerase cyclophilin 40 (CyP40) for reduction of neurotoxic fibrils and treatment and prevention of neurodegenerative diseases associated with amyloid fibril aggregation. Aspects of the invention include compositions, methods, dosage forms, and kits for treating or preventing a neurodegenerative disease or condition associated with amyloid fibril aggregation in a human or animal subject, and for disaggregating neurofibrillary aggregates in vitro or in vivo, using CyP40, or a biologically active fragment thereof.

The present invention concerns the use of peptidyl-prolyl isomerase cyclophilin 40 (CyP40) for reduction of neurotoxic fibrils and treatment and prevention of neurodegenerative diseases associated with amyloid fibril aggregation. Aspects of the invention include compositions, methods, dosage forms, and kits for treating or preventing a neurodegenerative disease or condition associated with amyloid fibril aggregation in a human or animal subject, and for disaggregating neurofibrillary aggregates in vitro or in vivo, using CyP40, or a biologically active fragment thereof.

The present invention concerns the use of peptidyl-prolyl isomerase cyclophilin 40 (CyP40) for reduction of neurotoxic fibrils and treatment and prevention of neurodegenerative diseases associated with amyloid fibril aggregation. Aspects of the invention include compositions, methods, dosage forms, and kits for treating or preventing a neurodegenerative disease or condition associated with amyloid fibril aggregation in a human or animal subject, and for disaggregating neurofibrillary aggregates in vitro or in vivo, using CyP40, or a biologically active fragment thereof.

Provided herein are modified caspase-9 polypeptides, and chimeric caspase-9 proteins containing the modified caspase-9 polypeptides. The disclosure further provides polynucleotides encoding these proteins, engineered host cells containing these polynucleotides and proteins, including host cells that co-express a chimeric antigen receptor, and methods of making and using the same.

Provided herein are modified caspase-9 polypeptides, and chimeric caspase-9 proteins containing the modified caspase-9 polypeptides. The disclosure further provides polynucleotides encoding these proteins, engineered host cells containing these polynucleotides and proteins, including host cells that co-express a chimeric antigen receptor, and methods of making and using the same.

A method of treating a cancer of the central nervous system in a subject in need thereof is provided. The method comprising administering to the subject a therapeutically effective amount of an agent which reduces blood glutamate levels and enhances brain to blood glutamate efflux to thereby treat the cancer of the central nervous system in the subject.

Provided are methods, compositions, and systems for targeted pseudouridylation of RNA. In some aspects, provided are methods for editing a target RNA (e.g., mRNA) in a host cell, comprising introducing an engineered guide small nucleolar RNA (gsnoRNA) into the host cell, wherein the gsnoRNA recruits a DKC1 protein to modify a target uridine residue into a pseudouridine residue in the target RNA. In some embodiments, the DKC1 protein has cytoplasmic localization in the host cell.

Provided are methods, compositions, and systems for targeted pseudouridylation of RNA. In some aspects, provided are methods for editing a target RNA (e.g., mRNA) in a host cell, comprising introducing an engineered guide small nucleolar RNA (gsnoRNA) into the host cell, wherein the gsnoRNA recruits a DKC1 protein to modify a target uridine residue into a pseudouridine residue in the target RNA. In some embodiments, the DKC1 protein has cytoplasmic localization in the host cell.