Described herein are methods of enhancing chromosomal homologous recombination to stimulate a loss of heterozygosity at a gene locus of interest in a living cell. These methods are driven by an enhancer component and a target-specific endonuclease component and proceed through a mechanism whereby: exogenous donor DNA that is homologous to the gene locus of interest is not introduced into the living cell; the desired allele of the gene locus of interest remains uncleaved; and the undesired allele is either uncleaved, cleaved at a single location, or cleaved at multiple locations. These methods have numerous applications, including the repair of risk alleles for disease prevention, the correction of heterozygous mutations in dividing cells, the design of cancer therapeutics, and the design of novel gene-drive strategies.

Described herein are methods of enhancing chromosomal homologous recombination to stimulate a loss of heterozygosity at a gene locus of interest in a living cell. These methods are driven by an enhancer component and a target-specific endonuclease component and proceed through a mechanism whereby: exogenous donor DNA that is homologous to the gene locus of interest is not introduced into the living cell; the desired allele of the gene locus of interest remains uncleaved; and the undesired allele is either uncleaved, cleaved at a single location, or cleaved at multiple locations. These methods have numerous applications, including the repair of risk alleles for disease prevention, the correction of heterozygous mutations in dividing cells, the design of cancer therapeutics, and the design of novel gene-drive strategies.

The present invention is drawn to novel methods of selecting mammals receptive to embryo transfers in order to improve reproductive efficiency and milk production of the mammals. The present invention encompasses three methods: (1) selecting from any group of mammals; (2) selecting from estrus-negative mammals; and (3) selecting from estrus-negative mammals and pooling the selected mammals with estrus-positive mammals. Also encompassed is a kit for selecting mammals receptive to embryo transfers.

The present invention is drawn to novel methods of selecting mammals receptive to embryo transfers in order to improve reproductive efficiency and milk production of the mammals. The present invention encompasses three methods: (1) selecting from any group of mammals; (2) selecting from estrus-negative mammals; and (3) selecting from estrus-negative mammals and pooling the selected mammals with estrus-positive mammals. Also encompassed is a kit for selecting mammals receptive to embryo transfers.

Artificial ovaries comprising porous three-dimensional scaffolds are provided. Also provided are ink compositions and methods for printing the scaffolds. The artificial ovaries have spatial arrangements and cellular compositions that allow them to mimic native ovarian tissue. As such, they can be cultured or transplanted to support female endocrine function and/or the development of oocytes and/or eggs.

Artificial ovaries comprising porous three-dimensional scaffolds are provided. Also provided are ink compositions and methods for printing the scaffolds. The artificial ovaries have spatial arrangements and cellular compositions that allow them to mimic native ovarian tissue. As such, they can be cultured or transplanted to support female endocrine function and/or the development of oocytes and/or eggs.

Compositions and methods comprising bioenergetic agents for restoring the quality of aged oocytes, enhancing oogonial stem cells or improving derivatives thereof (e.g., cytoplasm or isolated mitochondria) for use in fertility-enhancing procedures, are described.

Compositions and methods comprising bioenergetic agents for restoring the quality of aged oocytes, enhancing oogonial stem cells or improving derivatives thereof (e.g., cytoplasm or isolated mitochondria) for use in fertility-enhancing procedures, are described.

The purpose of the present invention is to provide immortalized stem cells, which produce a growth factor capable of regenerating various kinds of tissues that have been damaged by a variety of causes, and a method for producing the aforesaid immortalized stem cells. Another purpose is to provide a medicinal composition and a medicinal preparation for restoring damaged tissues, and a method for the percutaneous absorption of a culture supernatant. Provided are immortalized stem cells that are obtained by isolating stem cells selected from the group consisting of mammalian mesenchymal cells, an embryo at the early stage of the development and somatic cells, first culturing the cells to give first stage culture cells, transferring four kinds of genes into the first stage culture cells to give transgenic cells, and selecting the desired immortalized stem cells from among the transgenic cells using the expression of STRO-1 as an index.

The purpose of the present invention is to provide immortalized stem cells, which produce a growth factor capable of regenerating various kinds of tissues that have been damaged by a variety of causes, and a method for producing the aforesaid immortalized stem cells. Another purpose is to provide a medicinal composition and a medicinal preparation for restoring damaged tissues, and a method for the percutaneous absorption of a culture supernatant. Provided are immortalized stem cells that are obtained by isolating stem cells selected from the group consisting of mammalian mesenchymal cells, an embryo at the early stage of the development and somatic cells, first culturing the cells to give first stage culture cells, transferring four kinds of genes into the first stage culture cells to give transgenic cells, and selecting the desired immortalized stem cells from among the transgenic cells using the expression of STRO-1 as an index.