Abstract: Inhibitors of mismatch repair can be used to generate hypermutable cells and organisms. By inhibiting this process in cells, new cell lines and varieties with novel and useful properties can be prepared more efficiently than by relying on the natural rate of homologous recombination. These methods are useful for generating targeted loci that can alter the expression profiles of target genes as well as tag exons of a gene with a reporter marker to facilitate the monitoring of a given gene product when the host is grown under different conditions or exposed to biological and chemical entities.

Abstract: The use of mismatch repair (MMR) defective antibody producer cells offers a method to generate subclone variants with elevated protein production such as antibodies. Using MMR defective cells and animals, new cell lines and animal varieties with novel and useful properties such as enhanced protein production can be generated more efficiently than by relying on the natural rate of mutation. These methods are useful for generating genetic diversity within host cells to alter endogenous genes that can yield increased titer levels of protein production. By employing this method, two genes were discovered whose suppressed expression is associated with enhanced antibody production. Suppressed expression of these genes by a variety of methods leads to increased antibody production for manufacturing as well as strategies for modulating antibody production in immunological disorders. Moreover, the suppression of these two genes in host cells can be useful for generating universal high titer protein production lines.

Abstract: Whole Genome Evolution Technology can be considered a broad tool for supporting the needs for scaleable manufacturing of therapeutic antibodies. Its random nature and in vivo mode of action separate this process from other complementary technologies, thus providing alternative solutions to improve a host cell's manufacturing performance. The speed with which a pre-existing production strain can be optimized makes this process suitable for satisfying the current need for rapid cell line optimization to produce faster growing cells exhibiting high titers of antibody at the preclinical, clinical or commercialization stage.

Abstract: A human prolactin-binding protein and compositions and methods using this protein are provided.

Abstract: A human prolactin-binding protein and compositions and methods using this protein are provided.

Abstract: The use of mismatch repair (MMR) defective antibody producer cells offers a method to generate subclone variants with elevated protein production such as antibodies. Using MMR defective cells and animals, new cell lines and animal varieties with novel and useful properties such as enhanced protein production can be generated more efficiently than by relying on the natural rate of mutation. These methods are useful for generating genetic diversity within host cells to alter endogenous genes that can yield increased titer levels of protein production. By employing this method, two genes were discovered whose suppressed expression is associated with enhanced antibody production. Suppressed expression of these genes by a variety of methods leads to increased antibody production for manufacturing as well as strategies for modulating antibody production in immunological disorders. Moreover, the suppression of these two genes in host cells can be useful for generating universal high titer protein production lines.

Abstract: Inhibitors of mismatch repair can be used to generate hypermutable cells and organisms. By inhibiting this process in cells, new cell lines and varieties with novel and useful properties can be prepared more efficiently than by relying on the natural rate of homologous recombination. These methods are useful for generating targeted loci that can alter the expression profiles of target genes as well as tag exons of a gene with a reporter marker to facilitate the monitoring of a given gene product when the host is grown under different conditions or exposed to biological and chemical entities.

Abstract: The invention provides methods for generating antibiotic resistant bacteria comprising blocking mismatch repair in a bacterium to make hypermutable bacteria, contacting the bacteria with at least one antibiotic, selecting bacteria that are resistant to the antibiotic, and culturing the antibiotic resistant bacteria. The invention also provides methods of determining the genes responsible for antibiotic resistance.

Abstract: A human prolactin-binding protein and compositions and methods using this protein are provided.