Provided nucleic acid-based expression construct for the target cell-specific production of a therapeutic protein, such as a pro-apoptotic protein, within a target cell, including a target cell that is associated with aging, disease, or other condition, in particular a target cell that is a senescent cell or a cancer cell. Also provided are formulations and systems, including fusogenic lipid nanoparticle (LNP) formulations and systems, for the delivery of nucleic acid-based expression constructs as well as methods for making and using such nucleic acid-based expression constructs, formulations, and systems for reducing, preventing, and/or eliminating the growth and/or survival of a cell, such as a senescent cell and/or a cancer cell, which is associated with aging, disease, or other condition as well as methods for the treatment of aging, disease, or other conditions by the in vivo administration of a formulation, such as a fusogenic LPN formulation, comprising an expression construct for the target cell-specific production of a therapeutic protein, such as a pro-apoptotic protein, in a target cell that is associated with aging, disease, or other condition, in particular a target cell that is a senescent cell or a cancer cell.

The invention provides novel engineered CRISPR/Cas effector enzymes, such as Cas13 (e.g., Cas13e) that substantially maintain guide-sequence-specific endonuclease activity and substantially lack guide-sequence-independent collateral endonuclease activity compared to the corresponding wild-type Cas. Also provided are polynucleotides encoding the same, vectors or host cells comprising the polynucleotides or engineered Cas, and method of use, such as in RNA-based target gene transcript knock down.

The present disclosure relates generally to methods of inducing differentiation of pluripotent stem cells into enteric nitrergic neurons, and enteric nitrergic neurons produced by such methods. Also provided are used of such enteric nitrergic neurons for screening potential therapeutic agents suitable for preventing and/or treating enteric nervous system disorders, such as gastroparesis, esophageal achalasia, chronic intestinal pseudo-obstruction, and hypertrophic pyloric stenosis, and applications of such enteric nitrergic neurons in regenerative medicine, such as cell transplantation therapy, for preventing and/or treating enteric nervous system disorders.

The present disclosure relates to methods and compounds for reprogramming metabolism in one specific retinal and neuronal cell type leading to improved cell and tissue survival and function. In particular, the present disclosure relates to increasing PGC1α/Pgc1α or NRF2/Nrf2 or inhibiting HIF/Hif or KEAP1/Keap1 to reprogram metabolism and survival of cells in a variety of neurodegenerative conditions, and specifically those which cause blindness.

A method of restoring lysosomal function of retinal pigment epithelial (RPE) cells and a method of preventing and/or treating age-related macular degeneration (AMD), Stargardt's macular retinal degeneration, neurodegenerative disease, or diabetic retinopathy in a subject are provided. The methods comprise administering (i) a nucleic acid encoding a polypeptide comprising a constitutively active form of transcription factor EB (TFEB) or (ii) the polypeptide to a subject in need thereof. Associated polypeptides, nucleic acids, vectors, and compositions thereof also are provided.

The present invention provides a recombinant adeno-associated virus (rAAV) vector for treating a blood coagulation-related disease to provide a novel gene therapy means for hemophilia. The virus vector comprises a virus genome comprising a liver-specific promoter sequence and a polynucleotide sequence encoding a genome editing means operably linked to the promoter sequence, wherein the genome editing means is (a) a means comprising CRISPR/Cas9 composed of a Cas9 protein and a guide RNA (gRNA) and a repair gene, or (b) a means comprising CRISPR/Cas9 composed of a Cas9 protein and a gRNA, and the gRNA comprises a nucleotide region complementary to a part of a region related to expression of a disease-related protein on the genome of a patient and a region that interacts with the Cas9 protein.

The present invention relates to an animal model for oxidative stress research and use thereof, and more specifically, the present invention can utilize a mutant of RCAT having a regulatory function for an antioxidant stress regulator in Caenorhabditis elegans and a human cell line expressing RCAT as animal and human cell line models for oxidative stress research, using the mutant and the human cell line.

A non-human transgenic animal expressing ApoL1 is provided as well as a method for generating the same. Also provided is a method for identifying an agent capable of reducing the progression of an ApoL1 mediated nephropathy. Furthermore, an isolated antibody is provided which binds to the human variants of ApoL1.

Rat cells and rats comprising an inactivated Cfh locus and methods of making and using such rat cells and rats are provided. The rats comprising an inactivated Cfh locus model C3 glomerulopathy (C3G). Methods are provided for using such rats comprising an inactivated Cfh locus to assess in vivo efficacy of putative C3G therapeutic agents.

Provided is application of ECM1 in the prevention and/or treatment of liver fibrosis-related diseases, specifically provided is the use of ECM1 gene, or protein or a promoter thereof for preparing a composition or a formulation, the composition or formulation being used for (a) preventing and/or treating of liver fibrosis-related diseases; and/or for (b) maintaining liver homeostasis. The ECM1 gene, or the protein or promoter thereof can significantly (i) prevent and/or treat cirrhosis-related diseases; and/or (ii) maintain the liver homeostasis. In addition, the ECM1 gene, or the protein or promoter thereof can also significantly (i) inhibit the occurrence of liver fibrosis-related diseases; and/or (ii) inhibit the activation of hepatic stellate cells (HSCs).