Abstract: The present invention relates to chimeric viruses, the replication of which is regulated by a transactivation signal produced by diseased host cells. The chimeric viruses of the invention can infect both normal and diseased host cells. However, the chimeric virus replicates efficiently in and kills diseased host cells that produce the transactivation signal. The use of such chimeric viruses to treat infectious diseases and cancers are described. A particularly useful embodiment involves the modification of a murine parvovirus that infects human T cells to generate a chimeric parvovirus that is cytocidal to human T cells that express HIV-tat. The chimeric parvovirus can be used to treat HIV-infection.

Abstract: Disclosed are cells and methods for treating or preventing tumor formation or infections with pathogens in a patient. The cells of the invention are antigen-presenting cells (e.g., dendritic cells or macrophage) that have been loaded with RNA derived from tumors or pathogens. By administering the RNA-loaded antigen-presenting cells to a patient, tumor formation or pathogen infections can be treated or prevented. Alternatively, the RNA-loaded cells can be used as stimulator cells in the ex vivo expansion of CTL. Such CTL can then be used in a variation of conventional adoptive immunotherapy techniques.

Abstract: Methods of controlling the in vivo and in vitro expression of a heterologous protein by transfecting a cell with a first nucleic acid encoding the heterologous polypeptide, wherein at least one codon of mRNA transcribed from the first nucleic acid is replaced by the codon UGA, and a second nucleic acid operably linked to the first nucleic acid, the second nucleic acid directing the translation of the UGA codon as selenocysteine only when the cell can obtain selenium from the medium in which it is grown; and growing the cell under conditions in which the production of the polypeptide is controlled by the level of selenium available to the cell.

Abstract: This invention relates to a new and improved pharmaceutical composition and method for delivery of therapeutic or bioactive agents. The methods and composition of the invention can be used with several therapeutic or bioactive agents and can achieve site-specific delivery of a therapeutic or biologically-active substance. This can allow for lower doses and for improved efficacy with drugs, particularly agents such as oligonucleotides which are plagued with problems in achieving therapeutic levels at targeted sites.

Abstract: The present invention is directed to methods which employ inhibition of the post-translational hypusine formation in the intracelluar protein eIF-5A, for the purpose of suppressing infections by viruses that parasitize eIF-5A so as to promote their own replication. Intentional inhibition of the post-translational formation of hypusine in infected host cells with compounds generically termed `hypusine inhibitors` not only selectively suppresses the production of viral proteins and of infectious viral particles, but also causes, particularly after hypusine inhibitor withdrawal, apoptosis in such virally-infected cells.

Abstract: The invention relates to a composition including a targeting complex containing a component of an effector system and a ligand capable of targeting a cell surface marker in association with at least one further targeting complex containiing a further component of the effector system and a ligand capable of targeting a cell surface marker which is a different cell surface marker to that targeted by at least one of the other targeting complexes, wherein the desired activity of the effector system is dependent on the selective internalization and functional cooperation of the components thereof.

Abstract: An reproducible transformation system of a yeast of Candida utilis, a process for expressing a heterologous gene in the transformation system, a vector which can be used in the transformation system and the expression method, and a novel DNA group are disclosed. In particular, the process for expressing a heterologous gene in Candida utilis comprises transforming Candida utilis with a vector comprising a drug-resistance marker, a sequence homologous to the chromosomal DNA of the Candida utilis yeast, and the heterologous gene, culturing the transformant, and isolating the expression product of the heterologous gene.

Abstract: Methods for producing HAV cDNA, products thereof, and uses thereof, are described. HAV cDNA is produced, for example, by reverse transcribing HAV RNA and subsequently inserting the HAV cDNA into bacterial plasmids by genetic-engineering techniques. Transformed bacteria are then cloned and cultured to produce replicated chimeric plasmids containing the HAV cDNA. Such HAV cDNA is useful in assaying for the presence of HAV and in the production of HAV antigen and in the production of antibodies against HAV.

Abstract: The present invention provides a chimeric adenovirus fiber protein, which differs from the wild-type coat protein by the introduction of a nonnative amino acid sequence in a conformationally-restrained manner. Such a chimeric adenovirus fiber protein according to the invention is able to direct entry into cells of a vector comprising the chimeric fiber protein that is more efficient than entry into cells of a vector that is identical except for comprising a wild-type adenovirus fiber protein rather than the chimeric adenovirus fiber protein. The nonnative amino acid sequences encodes a peptide motif that comprises an epitope for an antibody, or a ligand for a cell surface receptor, that can be employed in cell targeting. The present invention also pertains to vectors comprising such a chimeric adenovirus fiber protein, and to methods of using such vectors.

Abstract: The present invention relates, in general to protein that is a seed storage protein having high nutritional value. In particular, the invention relates to the protein AmA1 and to a DNA sequence encoding same. The invention further relates to a recombinant molecule comprising the AmA1 encoding sequence and to a host cell transformed therewith. In addition, the invention relates to a method for producing transgenic plants with high nutritionally rich amino acids.

Abstract: An interactive computer program generates a composite dot matrix representation of secondary structure elements from a set of functionally related oligonucleotides. The composite image facilitates visual detection of conserved secondary structure motifs with similar sequence sets. The complete pattern displaying all possible base pairings can be readily pruned with two progressive filters to provide the user with a simplified figure displaying only the most stable and conserved regions. Additional simplification of the structure matrix image can be achieved by eliminating mutually exclusive structures. Alignment editing provided within the program facilitates refinement of the consensus secondary structure.

Abstract: Disclosed herein is the method for dramatically reducing cytotoxicity of viral vectors such as Herpes simplex viral while retaining gene expression. The method of the invention virtually eliminates the concern of possible recombination during virus propagation and contamination of wild-type virus and virus stock. The invention comprises use of photochemical crosslinking causing differential inactivation of viruses.

Abstract: The invention encompasses methods of maintaining desired recombinant genes in a genetic population of cells expressing the recombinant gene. The methods utilize mutant cells which are characterized by a lack of a functioning native gene encoding an enzyme which is essential for cell survival, wherein this enzyme catalyzes a step in the biosynthesis of an essential cell wall structural component and the presence of a first recombinant gene encoding an enzyme which is a functional replacement for the native enzyme, wherein the first recombinant gene cannot replace the defective chromosomal gene. The first recombinant gene is structurally linked to a second recombinant gene encoding a desired product. Loss of the first recombinant gene causes the cells to lyse when the cells are in an environment where a product due to the expression of the first recombinant gene is absent. The invention also encompasses methods of creating and isolating mutant cells with the above characteristics.

Abstract: Stable packaging cell lines derived from human 293 cells which are transfected with an AAV vector having the AAV rep gene operably line to a heterologous transcription promoter, such as the metallothionein promoter, or an AAV Rep78 insensitive homologous promoter and which are capable of producing AAV Rep proteins and being useful for packaging recombinant AAV vectors containing target polynucleotides.

Abstract: The present invention relates to a system for producing a protein of interest in a host cell comprising the combined use of two expression cassettes, one of which is for expressing a useful DNA fragment controlled by a thiamine-regulable promoter region, while the other is for expression an activator gene. The present invention also concerns expression cassettes comprising a useful DNA fragment controlled by a promoter region derived from the Schizosaccharomyces pombe pho-4 gene, as well as the vectors and cells comprising such an expression cassette. A novel method for the production of a useful protein is also provided.

Abstract: This invention relates to methods and compositions of controlling cell distribution within a bioartificial organ by exposing the cells to a treatment that inhibits cell proliferation, promotes cell differentiation, or affects cell attachment to a growth surface within the bioartificial organ. Such treatments include (1) genetically manipulating cells, (2) exposing the cells to a proliferation-inhibiting compound or a differentiation-inducing compound or removing the cells from exposure to a proliferation-stimulating compound or a differentiation-inhibiting compound; exposing the cells to irradiation, and (3) modifying a growth surface of the BAO with ECM molecules, molecules affecting cell proliferation or adhesion, or an inert scaffold, or a combination thereof. These treatments may be used in combination.

Abstract: An isolated DNA having a promoter activity in an animal cell; a method for expressing a useful gene using the isolated DNA; and a method for producing a protein in an animal cell using the isolated DNA. The present invention provides a method for producing a desired gene product in a large quantity in an animal cell.

Abstract: This disclosure relates to the n K.sup.+ channel expression product of the MK3 gene or a functionally bioactive equivalent thereof and its uses, particulary in combination with identifying immune responses and materials modulating or blocking same.

Abstract: Disclosed are methods that achieve i) site-directed delivery, ii) in situ amplification, and iii) sustained expression of an exogenous gene product within renal glomeruli. An exogenous gene, E. coli .beta.-galactosidase, was introduced into cultured rat mesangial cells using a replication-defective retrovirus, and stable infectants were administered to a rat kidney via the renal artery. In the injected kidney, the engineered, cultured mesangial cells populated 40% of glomeruli site-specifically. The gene product was detected throughout a 14-week period of observation. In an alternative method, engineered, cultured mesangial cells were injected into a kidney subjected to an antibody that induces mesangiolysis followed by mesangial regeneration. Under these conditions, expression of .beta.-galactosidase was dramatically amplified in situ and high level expression continued for at least 8 weeks.

Abstract: A novel system for cloning and expression of genes in gram-positive bacteria. The expression system is based on the finding that many gram-positive bacteria sort proteins to their cell surface through cis-acting N-terminal signal sequences and C-terminal anchor regions. In particular, the cell sorting signals of the streptococcal M6 protein, a well-known surface molecule, are used to construct a gram-positive expression system, designated SPEX (Streptococcal Protein Expression). Expression is achieved by cloning the gene of interest into an appropriate SPEX cassette which is then stably introduced into a bacterial host, such as the human commensal Streptococcus gordonii. Depending on the SPEX vector used, recombinant proteins can be anchored to the cell wall prior to release by specific endoproteolytic cleavage or secreted into the culture medium during bacterial growth. The use of host bacteria lacking extracellular proteases should protect secreted proteins from proteolytic degradation.