Provided herein is an in-series synthetic receptor circuit for dual-antigen AND-gate control over expression of a therapeutic payload by engineered cells. In some embodiments, the circuit may be composed of a first binding-triggered transcriptional switch, a second binding-triggered transcriptional switch and a therapeutic payload (e.g., a chimeric antigen receptor), where binding of the first binding-triggered transcriptional switch to a first antigen activates expression of the second binding-triggered transcriptional switch, and binding of the second binding-triggered transcriptional switch to a second antigen activates expression of the therapeutic payload. If the cell is an immune cell and the therapeutic payload is a chimeric antigen receptor, then the immune cell may be activated by binding of the chimeric antigen receptor to a third antigen. Methods of treatment using the cell also provided.

A method of treating a cancer in a mammalian subject with a tumor signature characterized by any one or more of (i) a level of sirtuin (SIRT3) protein that is below a first predetermined threshold level, (ii) a level of manganese superoxide dismutase acetylated at the lysine 68 residue (AcK68) that exceeds a second predetermined threshold level, and (iii) expression levels of hypoxia-inducible factor 2.sub.α (HIF2.sub.α) that exceed a third predetermined threshold level indicative of lineage plasticity for stemness, the method comprising administering to the mammalian subject a therapeutically effective amount of a pentaaza macrocyclic ring complex corresponding to the Formula (I) below, optionally with administration of a further anti-cancer therapeutic agent.

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The disclosure relates to double stranded ribonucleic acid (dsRNAi) agents and compositions targeting a SOD1 gene, as well as methods of inhibiting expression of a SOD1 gene and methods of treating subjects having a SOD1-associated neurodegenerative disease or disorder, e.g., Amyotrophic Lateral Sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD), and Down's syndrome (DS), using such dsRNAi agents and compositions.

A transcriptomic analysis of genes consistently upregulated in high producer clones were each evaluated for their ability to increase the production of a protein of interest. The products of these genes (metabolism influencing products (MIP)), such as actin, Erp27, Erp57, Foxa1, PPAR, Ca3, and Tagap, could be sub-categorized into different functional categories such as signaling, protein folding, cytoskeleton organization and cell survival.

The present invention relates to a biocompatible peptide inhibiting the aggregation of a β-amyloid protein, and more particularly, to a biocompatible peptide derived from superoxide dismutase 1 (SOD1) and specifically binding to β-amyloid, a β-amyloid aggregation inhibitor including the peptide, and a pharmaceutical composition for treating a β-amyloid aggregation-associated disease. The peptide of the present invention has a strong binding strength to β-amyloid, inhibits the formation of a β-amyloid protein aggregate, and prevents neural cell death, thereby treating a neurodegenerative disease such as Alzheimer's disease. In addition, since the peptide of the present invention does not have cytotoxicity, it has no side effect of disturbing an immune system.

Provided herein are systems comprising Class2, Type V CRISPR polypeptides, guide nucleic acids (gNA), and optionally donor template nucleic acids useful in the modification of a PCSK9 gene. The systems are also useful for introduction into cells, for example eukaryotic cells having mutations in the PCSK9 gene. Also provided are methods of using such CasX:gNA systems to modify cells having such mutations.

A transdermal peptide with a nuclear localization ability and having an amino acid sequence as shown in SEQ ID NO: 1 is disclosed. A fusion protein including a macromolecular protein with one end being linked to the transdermal peptide is also disclosed. The transdermal peptide can be used in the preparation of a medicament or a transdermal preparation for treating skin diseases. A medicament for treating a skin disease includes the transdermal peptide and a pharmaceutically acceptable excipient. The transdermal peptide enters the cells autonomously to locate in the nuclei, and can penetrate through the stratum corneum of the skin into cells in the dermis. The peptide is conveniently synthesized artificially and suitable for transdermal administration, and has a therapeutic potential via transdermal administration by carrying a drug for treating skin diseases.

Described herein are compounds and methods for tethering proteins. For example, dimers of proteins, including SOD1 and DJ-1, are described, where the dimers are formed by the covalent bonding of a cysteine on the first monomer to a cysteine on the second monomer via a cyclic disulfide linker. The covalently attached dimers exhibit increased stabilization.

Aspects of the present disclosure are drawn to methods of improving the expression of secreted cuproenzymes from host cells by manipulating the expression level of one or more proteins involved in copper transport in the host cell, e.g., membrane-bound copper transporting ATPases and soluble copper transporters. The present disclosure also provides compositions containing such improved host cells as well as products derived from the improved host cells that contain one or more cuproenzymes of interest.

Provided are novel human copper-zinc superoxide dismutase, also known as superoxide dismutase 1 or SOD1, specific antibodies as well as fragments, derivatives and variants thereof as well as methods related thereto. Assays, kits, and solid supports related to antibodies specific for SOD1 are also disclosed. The antibody, immunoglobulin chain(s), as well as binding fragments, derivatives and variants thereof can be used in pharmaceutical and diagnostic compositions for SOD1 targeted immunotherapy and diagnosis, respectively.