The present invention features a dual vector system for disrupting and replacing a target gene comprising a mutation (e.g., dominant, recessive mutation). Embodiments of the invention may also provide compositions comprising the dual vector system, and methods of using the dual vector system, including but not limited to methods of modifying the genome of a cell, methods of genomic editing, and methods of treating cells or a subject suffering from a genetic disease comprising a mutation.

The invention provides a genetically modified non-human animal that comprises in its genome unrearranged T cell receptor variable gene loci, as well as embryos, cells, and tissues comprising the same. Also provided are constructs for making said genetically modified non-human animal and methods of making the same. Various methods of using the genetically modified non-human animal are also provided.

The present invention relates to synthetic retinal ON-bipolar cell-specific promoter sequences and their use in therapeutic transgene delivery to the eye for the improvement and/or restoration of vision. The invention features metabotropic glutamate receptor 6 (mGluR6) promoters for an increased and more specific expression in ON-bipolar cells, in particular in cone ON-bipolar cells of the human macula.

Disclosed herein are methods for modulating hair growth and increasing hair follicle stem cell activation in an individual in need thereof. This includes administering an agent that modulates a Gas6-Tyro3-Axl-Mertk (TAM) interaction or pathway.

Described herein are transgenic mice for testing immunogenicity and protective efficacy of a wide variety of therapeutic agents and vaccines, determining allograft rejection, and developing monoclonal antibodies and generating hybridomas. Methods of generating a transgenic mouse is also described. Described herein are mouse models capable of expressing B cell, a T cell, a monocyte, a macrophage, a dendritic cell, a NK cell, a iNKT cell, an innate lymphoid cell, a microglia cell, a red blood cell, which can develop into a functional human immune system.

A vector system for expressing a transgene in a cell, the vector system comprising a first vector and a second vector, wherein: (a) the first vector comprises in a 5′ to 3′ direction: a promoter; an intron; a 5′ end portion of the transgene coding sequence (CDS); a splice donor sequence; and a first recombinogenic region; (b) the second vector comprises in a 5′ to 3′ direction: a second recombinogenic region; a splice acceptor sequence; and a 3′ end portion of the transgene CDS; wherein the 5′ end portion and the 3′ end portion together constitute the transgene CDS, and wherein the intron is not capable of homologous recombination with the splice donor sequence to excise the 5′ end portion of the transgene CDS.

The invention provides novel engineered CRISPR/Cas effector enzymes, such as Cas13 (e.g., Cas13d, Cas13e, or Cas13f) 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.

Transgenic non-human animal models for cellular senescence are provided herein, as are methods and materials for making and using the transgenic non-human animal models. For example, a p21-Cre mouse model for cellular senescence is provided herein.

The present invention relates to methods for treating patients having cancer or a premalignant or neoplastic condition. It is based, at least in part, on the discovery that a genome editing technique that specifically targets a fusion gene can induce cell death in a cancer cell other than a prostate cancer cell, e.g., a hepatocellular cancer cell, having the fusion gene. The present invention provides methods for treating cancer patients that include performing a genome editing technique targeting a fusion gene present within one or more cells of a subject to produce an anti-cancer effect.

Complexes comprising a nucleic acid-guided endonuclease, a sequence-specific targeting nucleic acid and an amphipathic helical peptide are provided. Compositions and methods for delivery of complexes comprising a nucleic acid-guided endonuclease, a sequence-specific targeting nucleic acid and an amphipathic helical peptide to mammals for both research and therapeutic use are provided. Methods of treating or reducing one or more symptoms of type 2 diabetes, prediabetes and/or gestational diabetes are provided.