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.

Cumulus cell (CC) gene expression is being explored as an additional method to morphological scoring to choose the embryo with the highest chance to pregnancy. The present invention relates to a novel method of identifying biomarker genes for evaluating the competence of a mammalian oocyte in giving rise to a viable pregnancy after fertilization, based on the use of live birth and embryonic development as endpoint criteria for the oocytes to be used in an exon level analysis of potential biomarker genes. The invention further provides CC-expressed biomarker genes thus identified, as well as prognostic models based on the biomarker genes identified using the methods of the present invention.

The present invention relates to the identification of a genomic integration site for heterologous polynucleotides in Chinese Hamster Ovary (CHO) cells resulting in high RNA and/or protein production. More specifically it relates to CHO cells comprising at least one heterologous polynucleotide stably integrated into the S100A gene cluster of the CHO genome and to methods for the production of said CHO cells. Further, the invention relates to a method for the production of a protein of interest using said CHO cell and to the use of said CHO cell for producing a protein of interest at high yield. Integration within these specific target regions leads to reliable, stable and high yielding production of an RNA and/or protein of interest, encoded by the heterologous polynucleotide.

An agent capable of promoting proliferation and differentiation of granulosa cells is disclosed which comprises a growth and differentiation factor-9 (GDF9) protein comprising a modified GDF9 polypeptide monomer which includes at least one amino acid substitution that enhances binding to and/or activation of activin-like kinase 4 and/or 5 receptor (ALK4/5). The agent is preferably provided in a mature dimeric form (eg comprising two monomers of the same modified GDF9 polypeptide monomer) and/or in a pro/mature complex form. The agent may be suitable for, inter alia, promoting oocyte maturation in vitro for use in assisted reproductive technologies.

Provided herein are cross-reactive antibodies (or antigen binding fragments thereof) that bind to human CTLA4, activatable antibodies that bind to human CTLA4, nucleic acid molecules encoding the same, pharmaceutical compositions thereof, and methods of their therapeutic use (e.g., for treatment of cancer).

The present invention relates generally to a three-dimensional cell and tissue culture system for the female reproductive tract. In particular provided herein the system includes individual female reproductive cultures in a dynamic microfluidic setting or integrated using a microfluidic microphysiologic system. In some embodiments, the present invention provides ex-vivo female reproductive tract integration in a three dimensional (3D) microphysiologic system.

An object of the present invention is to provide an animal cell with improved proliferation ability and survival rate, a method for producing the animal cell, and a method for producing a target protein formed of the animal cell. According to the present invention, there is provided an animal cell having a gene encoding a target protein and a foreign gene encoding an isovaleryl-CoA dehydrogenase, in which the isovaleryl-CoA dehydrogenase is overexpressed.

This disclosure provides a cell culture media extending material capable of releasing nutrients into the cell culture environment slowly overtime. In embodiments, this material is a part of a cell culture vessel. In embodiments, the material is a coating or a film on a surface of a cell culture material. In additional embodiments, the material is a surface upon which cells are cultured, such as a cell culture vessel or a microcarrier.

A method for culturing primary gynecological tumor cells and culture medium used therein. The method includes using mild cell dissociation reagents to treat a gynecological solid tumor tissue, to ensure the vitality of tumor cells in the tissue to the greatest extent; preparing a special serum-free medium, and using a suspension culture system to culture solid tumor cells derived from a gynecological tumor in vitro to ensure the normal expansion of tumor cells and eliminate interference from normal cells to the greatest extent. The primary gynecological tumor cell culture obtained by the method of the present invention can be used for various cell-based in vitro experiments, second-generation sequencing, construction of animal models, construction of cell lines and the like. It is foreseeable that this culture method has broad application prospects in the fields of gynecological tumor research and clinical diagnosis and treatment.

An object of the present invention is to provide a method for efficiently producing a heparin-like substance without using an animal-derived tissue. The present invention relates to a method for producing a heparin-like substance and the like, the method comprising: (1) preparing a mammalian cell that produces a heparin-like substance, (2) preparing a recombinant cell in which a gene that encodes an extracellular domain of syndecan is introduced into the mammalian cell that produces a heparin-like substance and is prepared in step (1), and (3) culturing the recombinant cell prepared in step (2) in a medium and collecting the heparin-like substance from the resulting culture supernatant.