Engineered transposons and methods of use thereof are provided. The transposons typically include an RNA component and a protein component. The RNA component can include, for example, a DNA targeting sequence, one or more protein binding motifs, and a nucleic acid sequence of interest to be integrated into a target DNA. The protein component is typically derived from a RLE LINE element protein and can include a DNA binding domain, an RNA binding domain, a reverse transcriptase, a linker domain, and an endonuclease. Pharmaceutical compositions and methods of use for introducing nucleic acid sequences into the genomes of cells are also provided.

The present invention belongs to the field of virology, in particular to the field of hepatitis B virus treatment. Provided are a model and a method for screening HBV cccDNA inhibitors. According to the screening model and the method, the detection of a split luciferase is used as an alternative index ofHBV cccDNA detection, and a cccDNA-targeted drug can be screened in high throughput.

The present specification relates to a transgenic animal and a transgenic embryo producing components of an engineered nuclease.

According to the disclosure of the present specification, the transgenic animal (or embryo) producing components of an engineered nuclease is a transgenic animal (or embryo) which includes a first cell having a genome including a first toolbox; and a second cell having a genome including a second toolbox, wherein the first toolbox and the second toolbox include at least one of a polynucleotide encoding an RNA-guided endonuclease and a polynucleotide encoding a guide nucleic acid that is able to specifically bind to a target site, respectively, wherein the first toolbox is present in a first locus of the genome of the first cell; the second toolbox is present in a second locus of the genome of the second cell; and the first locus is different from the second locus.

The invention provides inducible promoter systems and their components incorporating components of a tetracycline operon. By coordinating expression of different transcriptional units in these systems as a result of selection of promoters and/or linking the units into the same DNA molecule, these systems can achieve higher levels of expression of coding segments of interest, increased differential levels of expression between on- and off-states, and/or greater responsiveness to inducing agents than conventional systems.

The present invention provides methods and compositions for stable genetic modification of cultured mammalian cells. The genetic modifications can be used to produce cultured mammalian cells for therapeutic or diagnostic purposes.

Described herein are methods of generating a programmable multicellular organoid and/or a 3D organ-specific tissue. Also, described are the programmable multicellular organoid and/or a 3D organ-specific tissue produced by the described methods. Also, described herein are in vitro methods of generating functional human tissue construct.

The current disclosure provides recombinant adenoviral vectors and adenoviral genomes that can accommodate or that contain a large transposon payload, for instance a transposon payload of up to 40 kb. The adenoviral vectors and genomes can deliver the large transposon payload into a target genome, for instance for gene therapy.

The present invention provides methods and compositions for stable genetic modification of cultured mammalian cells. The genetic modifications can be used to produce- cultured mammalian cells for therapeutic of diagnostic purposes.

Disclosed are methods of eliminating at least on target cell in a subject, comprising administering to the subject an effective amount of a composition comprising a plurality of immune cells, wherein each immune cell of the plurality expresses one or more chimeric ligand receptor(s) (CLR(s)) that each specifically bind to a target ligand on the at least one target cell, wherein specifically binding of the one or more CLR(s) to the target activates the immune cell, and wherein the activated immune cell induces death of the target cell. Exemplary target cells include, but are not limited to, hematopoietic stem cells (HSCs).

A variety of different types of targeted transposome complexes are described herein that may be used to mediate sequence-specific targeted transposition of nucleic acids. Also described herein is a method of characterizing desired samples in a mixed pool of samples comprising both desired samples and unwanted samples comprising, to produce sequencing data from double-stranded nucleic acid, initially sequencing a library comprising a plurality of nucleic acid samples from a mixed pool, wherein each nucleic acid library comprises nucleic acids from a single sample and a unique sample barcode to distinguish the nucleic acids from the single sample from the nucleic acids from other samples in the library; analyzing the sequencing data and identifying unique sample barcodes associated with sequencing data from desired samples; performing a selection step on the library comprising enriching nucleic acid samples from desired samples and/or depleting nucleic acid samples from unwanted samples; and resequencing the nucleic acid library.