The present invention encompasses compositions and methods to create a whole chromosome regulatable kill switch to inactivate expression of one or more therapeutic genes expressed from a synthetic chromosome.

The field of the invention encompasses synthetic chromosome compositions and methods that allow single cell spatiotemporal analysis in response to differentiation cues and labeling of transplanted cells to monitor the fate and function of such cells in the patient recipient.

The invention relates to large-scale production of human antibodies by transgenic animals with high production of fully human IgG up to >10 g/L in sera with human IgG1 subclass dominancy. This invention also supports a feasibility of complex chromosome engineering for complicated genetic studies in non-murine mammalian species.

The present invention encompasses compositions and methods to allow one to deliver and express multiple genes from a biosynthetic pathway in a recipient cell via a synthetic chromosome.

A promoter activation sequence that allows for stable and efficient expression of a DNA of interest in a mammalian cell is provided. The promoter activation sequence has a nucleotide sequence represented by SEQ ID NO: 1, or a nucleotide sequence of 850 or more in a nucleotide sequence having 85% or higher sequence identity thereto. Also disclosed are an expression vector having the promoter activation sequence, a promoter, and a DNA of interest, a mammalian cell and a mammal including the expression vector.

Provided is a method for producing a human artificial chromosome vector with high safety by using a human cell. The method for producing a human cell comprising a human artificial chromosome vector comprises: substantially eliminating endogenous genes of long-arm and short-arm in a disomic human cell containing a pair of the homologous human chromosomes or a trisomic human cell containing trisomy of the homologous human chromosomes, from one of two chromosomes of the disomy or one or two of three chromosomes of the trisomy, thereby producing a cell population containing a human cell containing a human artificial chromosome vector comprising long-arm moiety and short-arm moiety substantially containing no endogenous gene, a human centromere, and a telomere; and collecting the human cell containing the human artificial chromosome vector from the cell population. As well as, the human cell comprises the human artificial chromosome vector.

The present invention encompasses compositions and methods to create a whole chromosome regulatable kill switch to inactivate expression of one or more therapeutic genes expressed from a synthetic chromosome.