Provided herein, in some embodiments, are methods, compositions, systems and kits that enable removal of heterologous nucleic acid from engineered cells.

The present disclosure generally relates to nucleic acid molecules for use in regulating gene expression. Disclosed herein include nucleic acid molecules containing one or more structural elements of the viral capsid enhancer operably linked to a coding sequence of a gene of interest. In some embodiments, the viral capsid enhancer comprises a Downstream Loop (DLP) from a viral capsid protein, or a variant of the DLP.

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.

A nucleic acid for the controlled expression of a nucleic acid encoding a pro-apoptotic protein in an individual, including: a regulatory polynucleotide including a minimal promoter and at least one AARE (amino acid response element) nucleic acid, the regulatory polynucleotide being activated in an individual upon consumption of a diet deficient in at least one essential amino acid; and a nucleic acid encoding a pro-apoptotic protein, which is placed under the control of the regulatory polynucleotide.

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.

A recombinant adeno-associated virus (AAV) having an AAV capsid and packaged therein a heterologous nucleic acid which expresses two functional antibody constructs in a cell is described. Also described are antibodies comprising a heavy chain and a light chain from a heterologous antibody. In one embodiment, the antibodies are co-expressed from a vector containing: a first expression cassette which encodes at least a first open reading frame (ORF) for a first immunoglobulin under the control of regulatory control sequences which direct expression thereof; and a second expression cassette which comprises a second ORF, a linker, and a third ORF under the control of regulatory control sequences which direct expression thereof, wherein the second and third ORF for a second and third immunoglobulin construct. The vector co-expressing these two antibody constructs is in one embodiment an AAV, in which the 5 and 3 ITRs flank the expression cassettes and regulatory sequences.

The present invention is directed to the cells, compositions and methods for the production of recombinant protein. In particular, the invention is directed to a production process for obtaining high levels of soluble recombinant CRM.sub.197 protein from E. coli. Cells preferably contain one or more mutations of disulfide reductase genes, so that disulfide reductase activity is reduced. The invention also relates to purification method for CRM.sub.197 as well as characterization of properly folded CRM.sub.197 protein.

The present disclosure relates to chimeric post-transcriptional regulatory elements (PRE) and vectors useful for expressing a protein in a cell. The PRE contains alpha, beta and optionally gamma subelements selected from different native PRE sequences and are discovered to be more potent than their native counterparts.

The present invention relates in some aspects to super-enhancers and related compositions, methods, and agents that are useful for modulating expression of cell type-specific genes that are required for maintenance of cell identity (e.g., embryonic stem cell identity) or maintenance of a disease state (e.g., cancer).

The present invention provides methods and compositions for labeling and/or targeting cells with increased calcium by providing a CREB reporter system. In addition, methods of treating disorders with activated cells such as brain disorders or cancer are also provided herein.