This invention provides a non-human vertebrate exhibiting a higher human liver cell growth rate, a higher human liver cell replacement rate, and higher histological-physiological human reproducibility than existing non-human vertebrates comprising the human liver transplanted therein and a method for producing such non-human vertebrate. Specifically, the method for producing a transgenic non-human vertebrate comprising human liver cells transplanted therein comprises transplanting human liver cells in a non-human vertebrate that has impaired or lowered immune reactions against humans in the presence of human IL-6 in vivo.

In one aspect, the invention relates to a method of loading exosomes with oligonucleotide cargo, by incubating an oligonucleotide comprising one or more hydrophobic modifications with a population of exosomes for a period of time sufficient to allow loading of the exosomes with the oligonucleotide. Exosomes loaded with hydrophobically modified oligonucleotide cargo, and uses thereof, are also provided.

Embodiments disclosed herein provide compositions, methods, and uses for recombinant vectors encoding Zika virus (ZIKV) protein subunits, and immunogenic compositions thereof. Certain embodiments provide recombinant vectors encoding ZIKV nonstructural protein 1 (NS 1), and optionally, ZIKV envelope (E) protein and premembrane (prM) protein. Other embodiments provide expression cassettes comprising a promoter operably linked to a polynucleotide that encodes the ZIKV NS 1 protein, and optionally ZIKV E and prM proteins. In some embodiments, the disclosed expression cassettes can be incorporated into a vector to produce a recombinant vector. Also provided are immunogenic compositions comprising one or more recombinant vectors described herein, and methods for inducing an immune response against ZIKV in a subject comprising administering to the subject an immunologically effective dose of an immunogenic composition of the present disclosure.

Genetically modified mice comprising a nucleic acid sequence encoding a human M-CSF protein are provided. Also provided are genetically modified mice comprising a nucleic acid sequence encoding a human M-CSF protein that have been engrafted with human cells such as human hematopoietic cells, and methods for making such engrafted mice. These mice find use in a number of applications, such as in modeling human immune disease and pathogen infection; in in vivo screens for agents that modulate hematopoietic cell development and/or activity, e.g. in a healthy or a diseased state; in in vivo screens for agents that are toxic to hematopoietic cells; in in vivo screens for agents that prevent against, mitigate, or reverse the toxic effects of toxic agents on hematopoietic cells; in in vivo screens of human hematopoietic cells from an individual to predict the responsiveness of an individual to a disease therapy, etc.

Non-human animals comprising a human or humanized DPP4 nucleic acid sequence are provided. Non-human animals that comprise a replacement of the endogenous Dpp4 gene with a human or humanized DPP4 gene, or non-human animals comprising a human or humanized DPP4 gene in addition to the endogenous Dpp4 gene are described. Non-human animals comprising a human or humanized DPP4 gene under control of human or non-human DPP4 regulatory elements is also provided, including non-human animals that have a replacement of non-human Dpp4-encoding sequence with human DPP4-encoding sequence at an endogenous non-human Dpp4 locus. Non-human animals comprising human or humanized DPP4 gene sequences, wherein the non-human animals are rodents, e.g., mice or rats, are provided. Methods for making and using the non-human animals are described.

Non-human animals, expressing humanized CD3 proteins are provided. Non-human animals, e.g., rodents, genetically modified to comprise in their genome humanized CD3 proteins are also provided. Additionally, provided are methods and compositions of making such non-human animals, as well as methods of using said non-human animals.

Genetically modified rodents such as mice and rats, and methods and compositions for making and using the same, are provided. The rodents comprise a humanization of at least one endogenous rodent Tmprss gene, such as an endogenous rodent Tmprss2, Tmprss4, or Tmprss11d gene.

The present invention relates to a method of treating, mitigating, minimizing, or preventing HIV-1/AIDS by administering a CD24 protein to a subject in need thereof. Also provided herein is use of a CD24 protein in the manufacture of a medicament for treating HIV-1/AIDS. Further, provided is a pharmaceutical composition comprising a pharmaceutically acceptable amount of a CD24 protein.

This disclosure provides peptides which have a strong affinity for the checkpoint receptor programmed death 1 (PD-1). These peptides block the interaction of PD-1 with its ligand PD-L1 and can therefore be used for various therapeutic purposes, such as inhibiting the progression of a hyperproliferative disorder, including cancer; treating infectious diseases; enhancing a response to vaccination; treating sepsis; and promoting hair re-pigmentation or lightening of pigmented skin lesions.

Various aspects described herein provide methods of generating alveolar or alveolar/airway organoids from a population of lung cells to differentiate into alveolar or alveolar/airway organoids. Also provided herein are methods and compositions for treating lung disease comprising transplantation of the alveolar or alveolar/airway organoids, or a cell isolated therefrom to a subject.