The present invention relates to nucleic acid expression cassettes that are engineered to enhance gene expression. Vectors and methods employing the expression cassettes containing novel chimeric regulatory elements are provided. The invention is particularly useful for delivery of transgenes to target cells and confers desirable properties for liver-directed and muscle-directed or liver-directed and bone-directed gene therapy. Moreover, the invention relates to a novel method of engineering tandem enhancer/promoter elements and expressing transgenes for example within liver and/or muscle cells, and delivery of therapeutics for treating various disorders.

The invention relates to nucleic acid constructs for expression in mice for the production of heavy chain only antibodies and V.sub.H domains, transgenic mice, related methods and uses.

An expression vector for mammalian cells includes a selection cassette with a nucleotide sequence encoding a glutamine synthetase, operably linked to a PGK promoter and a pA signal. The vector may include the EASE element which is known to promote stable integration of the expression cassettes into the genome. The vector also includes a selection cassette with a nucleotide sequence encoding an enzyme that confers resistance against an antibiotic to a bacterial host as a bacterial selection marker, operably linked to a suitable promoter. The vector further includes an expression cassette for a target polypeptide with an insertion site for a nucleotide sequence encoding the target polypeptide, operably linked to a. CMV promoter and a pA signal. The vector also includes a bacterial origin of replication.

The invention relates to nucleic acid constructs for expression in mice for the reproduction of heavy chain only antibodies and V.sub.H domains, transgenic mice, related methods and uses.

Compositions and methods are provided for Tat-inducible expression of a CRISPR-associated endonuclease by a truncated HIV LTR promoter containing at least a core region and a TAR region of a HIV LTR promoter. The compositions may be used as a therapeutic treatment for the treatment and/or prevention of HIV.

Provided is a polynucleotide, the polynucleotide can be used as a WXRE transcriptional regulatory element used to increase the protein expression level of a protein expression system. A protein expression vector or a protein expression system comprising the above-mentioned WXRE transcriptional regulatory element as well as the use thereof are also provided. The use of the WXRE transcriptional regulatory element can increase the expression level of a heterologous protein greatly with its biological activity unchanged.

A method, system, and apparatus for treating a patient with HIV. A vector can be modified from a thymidine kinase gene. The modified vector is expressed in the presence of tat RNA. The modified vector is then package and delivered to HIV-infected cells. The replication of HIV is inhibited by eliminating infected cells in the presence of Ganciclovir. Modified cells are then selected utilizing transient tat RNA transfection and GFP expression. Vector-modified stem cells are then selected for transplantation back into the patient, thereby producing a normal immune system in the patient when the modified vector remains dormant in the absence of HIV tat.

The present disclosure provides polynucleotide cassettes, expression vectors and methods for the expression of a gene in cone cells.

Disclosed herein are compositions and methods for treating cancer in a subject. This involves administering an oncolytic virus containing a heterologous DNA sequence encoding one or more immunomodulatory and/or immunostimulatory polypeptide(s) of interest to the subject under conditions effective to enhance an anti-tumor immune response in the subject, and to treat cancer. It also relates to a method of enhancing the delivery to and distribution within a tumor mass of therapeutic viruses.

In certain embodiments a lentiviral vector having an LCR comprising HS1 ENCODE core (EC1) sequence (SEQ ID NO:1), and one or more of an HS2 core sequence (ecHS2), an HS3 core sequence (ecHS3), an HS4 core sequence (ecHS4), a full length HS2, a full length HS3, and/or a full length HS4 sequence is provided. In certain embodiments the vector comprises a modified βAS3-globin transgene, where transgene comprises a codon optimized exon 1, and/or a codon optimized exon 2, and/or a codon optimized exon 3.