An isolated polynucleotide encoding a modified luciferase polypeptide and substrates. The OgLuc variant polypeptide has at least 60% amino acid sequence identity to SEQ ID NO: 1 and at least one amino acid substitution at a position corresponding to an amino acid in SEQ ID NO: 1. The OgLuc variant polypeptide has at least one of enhanced luminescence, enhanced signal stability, and enhanced protein stability relative to the corresponding polypeptide of the wild-type Oplophorus luciferase.

The present invention discloses a targeted exosome based on the RBD region of SARS-CoV-2 S protein and a preparation method thereof. An RBD-VSVG fusion protein is expressed on the targeted exosome of the present invention, and the RBD-VSVG fusion protein is obtained by replacing the extracellular region of VSVG with the RBD of the SARS-CoV-2 S protein. In the present invention, a targeted exosome capable of efficiently and tissue-specifically delivering a potential anti-SARS-CoV-2 medicine is constructed. The targeted exosome is used to encapsulate SARS-CoV-2 siRNA, to specifically inhibit the virus replication in tissues and organs. In a mouse animal model, tail vein injection of exosome encapsulated SARS-CoV-2 siRNA significantly inhibits virus replication in mouse lung tissue and alleviates symptoms such as pneumonia caused by virus infection.

The present disclosure relates to genetically modified non-human animals that express a human or chimeric (e.g., humanized) TNFR2, and methods of use thereof.

Disclosed are Pear 1 and, serving as a target of fibrotic diseases, applications in a medicament for treating human Pear 1-related diseases. Also disclosed are a Pear 1-targeting antibody or a mutant of same or a composition comprising same and applications thereof. Disclosed are a humanized Pear 1 transgenic mice model, a construction method for same, and applications thereof. The technical solution of the present invention regulates fibroblast activation and has broad application prospects in treating fibrotic diseases and accompanying debilitating diseases.

Provided herein are compositions and methods for regenerating retinal ganglion cells (RGCs) from retinal neuron cells by activating transcription factors such as one or more of Atoh7, Brn3B, Sox4, Sox11, or Ils1. The retinal neuron cells may be interneuron cells such as amacrine cells, horizontal cells, and bipolar cell. The regenerated RGCs can project axons into discrete subcortical brain regions and establish retina-brain connections. They can respond to visual stimulation and transmit electrical signals into the brain. Therefore, the regenerated RGCs can replace damaged or degenerated RGCs, thereby treating vision impairment or blindness. The methods are likewise applicable to degenerated, damaged, or aged RGCs to stimulate them to regrow functional axons, thereby rejuvenating these RGCs.

Provided are a donor vector having an exon-humanized gene in which only exon nucleotide sequences of a mouse gene are replaced with human exon nucleotide sequences, an ES cell in which a mouse endogenous gene is replaced with the donor vector, and a mouse crated by using the ES cell.

The present invention relates to a method of treating a tauopathy in a subject, a method of improving cognitive ability in a subject suffering from cognitive impairment associated with a tauopathy, a method of reducing tau aggregates and neurofibrillary tangles. The method comprises administering an agent which promotes phosphorylation of tau at threonine in the sequence SSPGSPGTPGSRSR of the tau; and/or introduces a phosphomimetic of a phosphorylated tau, wherein the phosphorylated tau is tau that has been phosphorylated at threonine in the sequence SSPGSPGTPGSRSR of the tau.

The invention discloses methods for the generation of chimaeric human—non-human antibodies and chimaeric antibody chains, antibodies and antibody chains so produced, and derivatives thereof including fully humanised antibodies; compositions comprising said antibodies, antibody chains and derivatives, as well as cells, non-human mammals and vectors, suitable for use in said methods.

The present invention relates to methods for producing a non-human animal, such as an avian, comprising a targeted germline genetic modification, the method comprising: (i) delivering a programmable nuclease to sperm; (ii) fertilizing an ovum with the sperm, and (iii) generating the animal from the ovum, wherein the nuclease introduces the genetic modification into DNA of the sperm and/or the ovum.

Non-human animal genomes, non-human animal cells, and non-human animals comprising a humanized TTR locus and methods of using such non-human animal genomes, non-human animal cells, and non-human animals are provided. Non-human animal cells or non-human animals comprising a humanized TTR locus express a human transthyretin protein or a chimeric transthyretin protein, fragments of which are from human transthyretin. Methods are provided for using such non-human animals comprising a humanized TTR locus to assess in vivo efficacy of human-TTR-targeting reagents such as nuclease agents designed to target human TTR. Methods are also provided for making such non-human animals comprising a humanized TTR locus.