Provided herein are engineered hepatitis B virus (HBV) molecular vaccine constructs. Vaccine constructs can also include ligand-inducible engineered gene switch systems for modulating expression of heterologous genes, such as a cytokines, in host cells.

Described herein are donor vectors and systems for use in in vivo dual recombinase-mediated cassette exchange. Also described are animal models for consistent, rigorous, and facile investigation of transgene expression. Further described are methods of screening for therapeutic drugs using these animal models, and methods of treatment.

Polynucleotides encoding peptides, proteins, enzymes, and functional fragments thereof are disclosed. The polynucleotides of the disclosure can be effectively delivered to an organ, such as the lung, and expressed within cells of the organ. The polyribonucleotides of the disclosure can be used to treat a disease or condition associated with a gene of the ATP-binding cassette (ABC) family, such as ABCA3.

The present disclosure provides codon optimized Factor VIII sequences, vectors, and host cells comprising codon optimized Factor VIII sequences, polypeptides encoded by codon optimized Factor VIII sequences, and methods of producing such polypeptides.

A novel transgene for use to produce a coronavirus vaccine is provided. The transgene encodes: i) an RNA polymerase promoter; ii) a 5′ UTR; iii) a secretory sequence; iv) a coronavirus spike protein component, wherein the spike protein component incorporates a variant sequence at amino acid position 614 of a native spike protein; and v) a 3′ UTR and poly A sequence. A vaccine is also provided comprising the transgene or an mRNA transcript thereof.

The present invention pertains to a non-human genetically modified animal with increased susceptibility to infection with a human virus. The invention suggests to genetically impair the expression of newly identified viral infection repression factors CD302, Cr11, Ndufc2, AW112010, Scarb2 and Zc3hav1, which markedly improves infection with human viruses in none-human hosts. Furthermore provided are methods for the generation of the animal of the invention, methods for increasing or reducing the susceptibility of a cell to viral infection, methods for screening novel modulators of viral infection as well as new therapy options for the treatment of viral diseases, in particular hepatitis C.

Provided are engineered B lymphocytes modified to express one or several different types of microRNAs or anti-miRs where in one embodiments the lymphocytes contain multiple copy numbers of nucleic acids encoding the one or several different types of miRs or anti-miRs. Provided are compositions and methods for treating, ameliorating, or preventing a cancer cell, a breast cancer cell or a triple negative breast cancer, or a breast cancer cell that tests negative for estrogen receptors, progesterone receptors, or HER2, comprising or by administering a composition, formulation or pharmaceutical composition comprising a microRNA or anti-miR. Provided are methods for treating an inflammation, a disease, a condition, infection or cancer capable of being treated by modulation or inhibition or expression of an miRNA or anti-miRs by administering to an individual in need thereof a B lymphocyte that secretes a microRNA or anti-miR, or a B lymphocyte supernatant, extracellular vesicle or exosome having a microRNA or anti-miR.

The present disclosure generally relates to viral-based expression systems suitable for the production of molecules of interest. The disclosure relates to nucleic acid constructs, such as expression vectors, containing a modified replicon RNA which includes a modified 5′-unstranslated region (5′-UTR) and, optionally, at least some of its original viral sequence encoding structural proteins having been deleted. Also disclosed are methods for producing polypeptides of interest.

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.

Provided herein are pharmaceutical compositions (e.g., formulations) that can provide for the long-term stability of AAV vectors. Also provided herein are methods of making and using the pharmaceutical compositions. The pharmaceutical compositions provided by the present disclosure generally comprise an AAV, histidine, a stabilizing agent, a salt, and a surfactant.