Abstract: A transcriptomic analysis of genes consistently upregulated in high producer clones were each evaluated for their ability to increase the production of a protein of interest. The products of these genes (metabolism influencing products (MIP)), such as actin, Erp27, Erp57, Foxa1, PPAR, Ca3, and Tagap, could be sub-categorized into different functional categories such as signaling, protein folding, cytoskeleton organization and cell survival.

Abstract: Disclosed are cells that have stably integrated into their genomes exogenous nucleic acid sequences, such as transgenes, within or proximal to the integration site of a sequence comprising at least part of an endogenous retrovirus (ERV) or a LTR-retrotransposon (LTR-RT), or instead of a sequence encompassing an ERV or a LTR-RT that is part or was part of the genome of the cell, as well as method of producing and using such cells. Advantageously, a high level and/or stable production of the transgene expression product(s) can be achieved. Transgene integration and expression may be furthered by modulating the DNA repair pathways of the cell, e.g., by transiently expressing a gene encoding a protein that forms part of a DNA repair pathway during transgene integration.

Abstract: The present invention relates to purified and isolated DNA sequences having protein production increasing activity and more specifically to the use of matrix attachment regions (MARs) for increasing protein production activity in a eukaryotic cell. Also disclosed is a method for the identification of said active regions, in particular MAR nucleotide sequences, and the use of these characterized active MAR sequences in a new multiple transfection method.

Abstract: Disclosed herein are methods of genome alteration, in particular genome editing in eukaryotic cells (e.g., mammalian cells), preferably, but not exclusively the integration of exogenous nucleic acids into the genome of a cell or a population of cells. Such methods include the modulation of cell cycle phases via external conditions such as physical separation, temperature, exposure to certain substances such as cell cycle modulators. Genome alteration is also effected via the use of enzymes such as nucleases and nickases and/or the modulation of DNA repair pathways.

Abstract: The present invention relates to purified and isolated DNA sequences having protein production increasing activity and more specifically to the use of matrix attachment regions (MARs) for increasing protein production activity in a eukaryotic cell. Also disclosed is a method for the identification of said active regions, in particular MAR nucleotide sequences, and the use of these characterized active MAR sequences in a new multiple transfection method.

Abstract: Disclosed are eukaryotic expression systems and methods for the selection of mammalian cell lines that produce proteins of interest, such as therapeutic proteins. The systems and methods allow for a simple and fast selection of cells mediating high levels of recombinant protein production. The systems and methods decrease the efforts and time needed to bring a new therapeutic protein to the patients, and also lower the cost of the therapeutic protein by increasing the productivity of cells in a bioreactor.

Abstract: The present invention relates to purified and isolated DNA sequences having protein production increasing activity and more specifically to the use of matrix attachment regions (MARs) for increasing protein production activity in a eukaryotic cell. Also disclosed is a method for the identification of said active regions, in particular MAR nucleotide sequences, and the use of these characterized active MAR sequences in a new multiple transfection method.

Abstract: The invention discloses a method for selecting cells depending on their level of displaying and preferably secreting a protein of interest from a population of heterogeneously expressing cells, comprising: (a) contacting said cells with magnetic beads coated with an affinity group to the said cells, (b) mixing the said magnetic beads with the cells to capture the cells displaying/secreting the protein of interest, (c) performing at least one washing step to remove the non-captured cells, and (d) recovering the cells to which that magnetic beads have bound.

Abstract: The present invention relates to purified and isolated DNA sequences having protein production increasing activity and more specifically to the use of matrix attachment regions (MARs) for increasing protein production activity in a eukaryotic cell. Also disclosed is a method for the identification of said active regions, in particular MAR nucleotide sequences, and the use of these characterized active MAR sequences in a new multiple transfection method.

Abstract: Disclosed are methods and eukaryotic host cells for transgene expression. The cells may be treated and/or modified to increase homologous recombination (HR), decrease non homologous end joining (NHEJ) and/or to enhance a HR/NHEJ ratio in said cell. Such cells can be transfected with vectors comprising the transgene, which advantageously integrates into the genome of the cell to form a concatemeric structure which may comprise more than 200 transgene copies. Certain expression enhancing elements such as MARs are advantageously provided to further enhance and/or facilitate transgene expression. Disclosed is also a recombinant eukaryotic host cell, in particular a non-primate host cell, comprising a transgenic sequence encoding a protein and/or a RNA, in particular a primate protein and/or RNA, involved in translocation across the ER membrane and/or secretion across the cytoplasmic membrane.

Abstract: The present invention relates to purified and isolated DNA sequences having protein production increasing activity and more specifically to the use of matrix attachment regions (MARs) for increasing protein production activity in a eukaryotic cell. Also disclosed is a method for the identification of said active regions, in particular MAR nucleotide sequences, and the use of these characterized active MAR sequences in a new multiple transfection method.

Abstract: Isolated and purified MAR sequences of human and non-human animal origin are disclosed as are nucleotide sequences corresponding to or based on them. In particular, MARs and MAR constructs with high transcription and/or protein production enhancing activities are disclosed and so are methods for identifying such MARs, designing such MAR constructs and employing them, e.g., for high yield production of proteins.

Abstract: The present invention relates to purified and isolated DNA sequences having protein production increasing activity and more specifically to the use of matrix attachment regions (MARs) for increasing protein production activity in a eukaryotic cell. Also disclosed is a method for the identification of said active regions, in particular MAR nucleotide sequences, and the use of these characterized active MAR sequences in a new multiple transfection method.

Abstract: The present invention relates to compositions and methods for transfecting eukaryotic cells with nucleic acid vectors. In particular, the invention relates to the uses of Matrix Attachment Region (MAR) elements to increase stable and transient transfection efficiency.

Abstract: The present invention relates to compositions and methods for transfecting eukaryotic cells with nucleic acid vectors. In particular, the invention relates to the uses of MAR elements to increase stable and transient transfection efficiency.