Abstract: Proteins to be stabilized are incorporated between two domains of the gene III protein of a bacteriophage. A mixture of phages with a large repertoire of mutants of the protein to be stabilized in the gene III protein is treated with proteases. The phages which present the least stable variants of the protein lose their infectivity fastest, whereas those whose genes code for stabilized variants of the protein retain their infectivity longest. Infection of bacterial cells with the phages treated with proteases and multiplication thereof leads to enrichment of the phages which comprise genes of stabilized variants of the mutagenized protein. The sequences of the most stable variants of the protein are obtained in this way from the genomes of the phages remaining after several rounds of phage cultivation, proteolysis and reinfection.

Abstract: The present invention relates to a method for using viral vectors to bear populations of sequence variants and using plant hosts to select the sequences that exhibit the desired traits.

Abstract: Nucleic acid constructs for expressing an effector gene, with the nucleic acid construct comprising a promoter I (component a) which controls the expression of a transcription factor gene (component b), a transcription factor gene (component b), a promoter II (component c) to which the gene product of the transcription factor gene binds and which controls the expression of an effector gene (component d), and effector gene (component d), wherein the activity of the gene product of the transcription factor gene depends on one or more cellular regulatory proteins which bind to this gene product and affect its activity, and isolated cells containing the nucleic acid constructs, can be used for preparing a drug for treating diseases and in methods of treating diseases.

Abstract: The present invention provides a recombinant protein having an amino terminus of an adenoviral fiber protein and having a trimerization domain. A fiber incorporating such a protein exhibits reduced affinity for a native substrate than does a wild-type adenoviral fiber trimer. The present invention further provides an adenovirus incorporating the recombinant protein of the present invention.

Abstract: The present invention provides improved adenovirus vectors and packaging cell lines. One type of improved adenoviral vector comprises deletions within the E2b region of the adenoviral genome. These E2b-deleted virus are used in conjunction with novel cell lines that constitutively express E2b gene products. The present invention further provides adenoviral vectors deleted for all viral coding regions. These “gutted” vectors permit the transfer of large genes to cells as demonstrated herein by the transfer of the dystrophin gene to the muscle of mice. The E2b-deleted vectors and the gutted vectors provide improved adenoviral vectors useful for a wide variety of gene therapy applications.

Abstract: The present invention relates to a recombinant organism, and a bacterial strain such as Staphylococcus, and S. aureus, in particular. The organism has a regulatable gene for encoding an RNA polymerase specificity factor required for expression of at least one gene essential for growth of the organism. The regulatable gene is one which is responsive to an exogenous effector molecule, and may in particular be an inducer-responsive gene including an operator site, such as a lac operator, to which a repressor, such as a lacl-encoded repressor, is capable of binding. The regulatable gene may in particular be an IPTG responsive plaC allele.

Abstract: The present invention relates to improved retroviral vectors for gene therapy. In this invention, retroviral vectors with higher safety and efficiency are constructed from MLV-based starting vectors, MON and MIN.

Abstract: The invention concerns a process for the production of muteins of eukaryotic polypeptides in eukaryotic cells by means of homologous recombination. The invention additionally concerns a process for the production of human cells which are suitable for the production of human mutated proteins. Finally the invention concerns the human cells produced by the process and mutated human proteins obtainable therefrom as well as pharmaceutical preparations which contain these muteins.

Abstract: A DNA encoding 20K hGH is connected directly to a gene encoding Escherichia coli OppA protein secretion signal, or a modified form thereof, and a DNA encoding signal peptidase 1 to construct a recombinant plasmid, E. coli is transformed by the plasmid and cells of the resulting E. coli transformant strain are cultured for secretory production of the 20K hGH in the E. coli periplasm. This method enables efficient secretory production of 20K hGH and easy isolation and purification of 20K hGH from the periplasm fraction because the level of impure proteins in the E. coli periplasm is low.

Abstract: A system has been constructed which is suitable for tetracycline-inducible gene expression in Gram-positive bacteria such as Staphylococcus aureus and Bacillus subtilis. The replicon/host gene expression system is tightly regulated, can be used in complex as well as minimal media, and can produce a high level of gene expression upon induction, with a variety of gene products. The gene expression system is suitable for production of products toxic to the host cells, and can be used, for example, for the analysis of gene expression and gene products in Gram-positive bacteria, and in a test of the effect of a peptide or polypeptide inhibitor of an S. aureus enzyme on the growth of S. aureus cells in culture or during infection of an animal.

Abstract: The present invention is directed to a method of producing attenuated forms of bovine viral diarrhea (BVD) virus by mutating the Npro protease gene. The invention includes the attenuated viruses made by this method, antibodies generated using these viruses, and vaccines that can be used for immunizing cattle.

Abstract: The present invention is directed to a method of producing attenuated forms of bovine viral diarrhea (BVD) virus by mutating the Npro protease gene. The invention includes the attenuated viruses made by the method, antibodies generated using these viruses, and vaccines that can be used for immunizing cattle.

Abstract: The invention relates to a fed-batch fermentation process which uses special E. coli host/vector systems for the purpose of efficiently forming recombinant proteins, in particular recombinant antibody molecules, preferably antibody fragments such as miniantibodies. Under the given conditions, the E. coli cells are able to grow at a maximum specific growth rate up to very high cell densities. After the recombinant product formation has been switched on, it is only the formed product which restricts growth; there is no growth restriction due to substrates or metabolic by-products. High space-time yields of recombinant proteins can be achieved in this manner.

Abstract: An expression library comprising a repertoire of nucleic acid sequences cloned from a non-immunized source, each nucleic acid sequence encoding at least part of a variable domain of a heavy chain derived from an immunoglobulin naturally devoid of light chains (VHH) wherein the extent of sequence variability in the library is enhanced compared to the corresponding naive expression library by introducing mutations in one or more of the complementarity determining regions (CDRs) of the nucleic acid sequences or by generating alternative combinations of CDR and framework sequences not naturally present in the naive library repertoire. Also disclosed is the use of such a library in preparing antibodies, more particularly antibody fragments.

Abstract: Aortic-preferentially-expressed gene-1 (APEG-1) and striated muscle preferentially expressed (SPEG) polypeptide, DNA sequences encoding and controlling the transcription of the APEG-1/SPEG encoding gene, methods of diagnosing vascular injury, methods of conferring smooth muscle-cell specific expression, and methods of inhibiting vascular smooth muscle cell proliferation by increasing the level of APEG-1 at the site of vascular injury.

Abstract: Methods for modulating production of a T helper type 2 (Th2)-associated cytokine, in particular interleukin-4, by modulating the activity of a transcription factor, in particular the proto-oncoprotein c-Maf, that regulates expression of the Th2-associated cytokine gene are disclosed. Methods for modulating development of T helper type 1 (Th1) or T helper type 2 (Th2) subsets in a subject using agents that modulate transcription factor activity are also disclosed. The methods of the invention can further involve use of agents that modulate the activity of additional transcription factors that contribute to the regulation of Th1- or Th2-associated cytokines, such as a Nuclear Factor of Activated T cells (NF-AT) protein and/or an AP-1 family protein. Compositions for modulating Th2-associated cytokine production, recombinant expression vectors and host cells, as well as screening assays to identify agents that modulate c-Maf activity, are also disclosed.

Abstract: E. coli plasmids pMUT 1 and pMUT 2 containing DNA sequences exhibiting significant homologies to reduplicaton starting positions of other enterobacterial plasmids are disclosed. Also disclosed are expression vectors containing plasmicis pMUT1 and pMUT 2.

Abstract: The present invention provides a method of in vitro propagation of a viral eukaryotic gene transfer vector comprising a deleterious, i.e., a cytostatic, cytotoxic, or apoptotic, gene in a eukaryotic, e.g., a mammalian, host-production cell, comprising a blocking gene. The blocking gene inhibits the adverse effects of the deleterious gene on the eukaryotic host-production cell. Vectors and cells useful in the context of the present inventive method are also provided.

Abstract: The invention relates to herpesvirus saimiri viruses that are genetically modified by mutations and/or deleting specific essential and non-essential genes. The essential genes are required in replication of viral genes and are needed for viral proliferation. The non-essential genes can represent sites for the insertion of heterologous genetic material.

Abstract: A novel zinc finger transcription factore (RFLAT-1) and polypeptides related thereto, as well as nucleic acid compositions encoding the same, are provided. The subject polypeptide and nucleic acid compositions find use in a variety of applications, including diagnostic and therapeutic agent screening applications, as well as in treatment therapies. Also provided are methods of treating disease conditions associated with RANTES function, e.g. inflammation, and the like.