Abstract: The subject invention provides materials and methods for efficient, specific reduction or elimination of unwanted mRNA. These materials and methods can be used in therapies for retinal diseases. In one embodiment, ribozymes which degrade mutant mRNA are used to treat retinitis pigmentosa.

Abstract: The invention provides recombinant nucleic acids comprising nucleic acid sequences from the genomic DNA methyltransferase gene. The invention further provides sequence information for such nucleic acid sequences. In addition, the invention provides antisense oligonucleotides complementary to special regions of the genomic DNA methyltransferase gene or its RNA transcript. Finally, the invention provides methods for using such antisense oligonucleotides as analytical and diagnostic tools, as potentiators of transgenic plant and animal studies and gene therapy approaches, and as potential therapeutic agents.

Abstract: The present invention relates to methods of inhibiting infection by RNA viruses with complexes of an activator of RNase L and an oligonucleotide that is capable of binding to the genome, antigenome or mRNAs of a negative strand RNA virus to specifically cleave the genomic or antigenomic RNA strand of the virus. In accordance with the present invention, the methods and complexes of the invention may be applied to target any negative strand RNA virus. The invention in one embodiment relates to a covalently linked complex of an oligonucleotide that is capable of binding to the genomic or antigenomic template RNA strand of a negative strand RNA virus and/or binding to an mRNA of a viral protein (an “antisense oligonucleotide”) coupled to an activator of RNase L. In a preferred embodiment of the present invention, the oligonucleotide component of the complex is complementary to a region of the viral genomic RNA strand characterized by repeated or consensus sequences.

Abstract: The present invention is based on the finding that nucleic acids containing at least one unmethylated cytosine-guanine (CpG) dinucleotide affect immune responses in a subject. These nucleic acids containing at least one unmethylated cytosine-guanine (CpG) dinucleotide can be used to treat pulmonary disorders having an immunologic component, such as a response to inhaled lipopolysaccharide. The invention provides methods of treating subjects who have or are at risk of having these pulmonary disorders, and methods of altering the immunological components of the pulmonary disorders. The invention also provides pharmaceutical compositions for treating pulmonary disorders that have an immunologic component.

Abstract: The present invention provides a conditionally replicating viral vector, methods of making, modifying, propagating and selectively packaging, and using such a vector, isolated molecules of specified nucleotide and amino acid sequences relevant to such vectors, a pharmaceutical composition and a host cell comprising such a vector, the use of such a host cell to screen drugs. The methods include the prophylactic and therapeutic treatment of viral infection, in particular HIV infection, and, thus, are also directed to viral vaccines and the treatment of cancer, in particular cancer of viral etiology. Other methods include the use of such conditionally replicating viral vectors in gene therapy and other applications.

Abstract: New sub-monomer synthetic methods for the preparation of peptide nucleic acid oligomeric structures are disclosed that provide for the synthesis of both predefined sequence peptide nucleic acid oligomers as well as random sequence peptide nucleic acid oligomers. Further these methods also provide for the incorporation of peptide nucleic acid units or strings of such units with amino acids or strings of amino acids in chimeric peptide nucleic acid-amino acid compounds. Further disclosed are methods of making random libraries of peptide nucleic acids using the fully preformed monomers.

Abstract: Method and compositions are provided for the determination of telomere length and telomerase activity, as well as the ability to inhibit telomerase activity in the treatment of proliferative diseases. Particularly, primers are elongated under conditions which minimize interference from other genomic sequences, so as to obtain accurate determinations of telomeric length or telomerase activity. In addition, compositions are provided for intracellular inhibition of telomerase activity.

Abstract: The present invention discloses a process for improving the efficiency of feed utilization and/or for promoting the growth of animals in which an animal is fed a diet which comprises a composition comprising feed substance and a ready for use phospholipase additive. Preferably said composition also comprises at least one phospholipid. Said compositions are used to improve fat digestibility and to promote growth of the animal. The phospholipid is preferably lecithin and the preferred phospholipase is a mammalian phospholipase A2. In a preferred embodiment the phospholipase is produced using recombinant DNA technology to express the enzyme in a suitable host such as a microorganism or a transgenic plant.

Abstract: Nucleic acid catalysts, method of screening/selection for nucleic acid catalysts, synthesis of ribozyme libraries and discovery of gene sequences involved in a biological process are described.

Abstract: Compositions of chitosan-based compounds and nucleic acid or oligonucleotide which are capable of delivery to a cell. Methods of preparation of the compositions. Methods of administering the compositions in vitro to cells in culture or in vivo to an organism.

Abstract: The present invention provides a nucleotide sequence encoding carbamoyl phosphate synthetase II of Plasmodium falciparum. Carbamoyl phosphate synthetase II catalyses the first committed and rate-limiting step in the de novo pyrimidine biosynthetic pathway. P. falciparum relies exclusively on pyrimidine synthesis de novo because of its inability to salvage pyrimidines. Mature human red blood cells, however, have no recognized requirement for a pyrimidine nucleotide. Accordingly, this enzyme represents a prime chemotherapeutic locus. The present invention relates to the use of the sequence encoding carbamoyl phosphate synthetase II in the recombinant production of carbamoyl phosphate synthetase II and to antisense molecules, ribozymes and other gene inactivation agents designed from this sequence.

Abstract: The present invention provides a superior method of diagnosing Chronic Pelvic Pain Syndrome in men comprising measuring levels of cytokines in semen or components or fractions of semen. The invention also provides a method of treating a condition associated with elevated levels of a cytokine, such as TNF-&agr;, in semen or a component or fraction thereof, comprising administering a therapeutically effective amount of an ant-cytokine compound or composition, such as an anti-TNF-&agr; compound or composition.

Abstract: A method for in vitro mutagenesis and recombination of polynucleotide sequences based on polymerase-catalyzed extension of primer oligonucleotides is disclosed. The method involves priming template polynucleotide(s) with random-sequences or defined-sequence primers to generate a pool of short DNA fragments with a low level of point mutations. The DNA fragments are subjected to denaturization followed by annealing and further enzyme-catalyzed DNA polymerization. This procedure is repeated a sufficient number of times to produce full-length genes which comprise mutants of the original template polynucleotides. These genes can be further amplified by the polymerase chain reaction and cloned into a vector for expression of the encoded proteins.

Abstract: Oligonucleotides and oligonucleotide analogs are provided which are capable of antisense interaction with messenger RNA of papillomavirus. Such oligonucleotides or oligonucleotide analogs can be used for diagnostics and therapeutics as well as for research purposes. In accordance with preferred embodiments of this invention, oligonucleotide or oligonucleotide analog is provided which is hybridizable with a messenger RNA from a papillomavirus. The oligonucleotide or oligonucleotide analog is able to inhibit the function of the RNA, and accordingly is useful for therapy for infections by such papillomavirus. In accordance with a preferred embodiment, portions of the papillomavirus are targeted for antisense attack. Thus oligonucleotides are preferably provided which hybridize with the E2, E1, E7, E6 or E6-7 messenger RNAs.

Abstract: An improvement in adaptor-based sequence analysis is provided that addresses the problems created by self-ligation of target polynucleotides that have complementary ends. The improvement includes preparation of target polynucleotides with dephosphorylated 5′ strands and the use of adaptors having a 3′ blocking group. In a preferred embodiment, adaptors are ligated to target polynucleotides by a single strand, 3′ blocking groups are removed, the adjacent 5′ hydroxyl of the target polynucleotide is phosphorylated, and the ligation of the adaptor is completed by treatment with a ligase.

Abstract: The present invention provides a conditionally replicating viral vector, methods of making, modifying, propagating and selectively packaging, and using such a vector, isolated molecules of specified nucleotide and amino acid sequences relevant to such vectors, a pharmaceutical composition and a host cell comprising such a vector, the use of such a host cell to screen drugs. The methods include the prophylactic and therapeutic treatment of viral infection, in particular HIV infection, and, thus, are also directed to viral vaccines and the treatment of cancer, in particular cancer of viral etiology. Other methods include the use of such conditionally replicating viral vectors in gene therapy and other applications.

Abstract: A bacterial strain of Escherichia coli BKIIM B-3996, a producer of L-threonine, containing a recombinant plasmid pVIC40 and deposited on Nov. 19, 1987 in the collection of microorganism cultures at the USSR Antiobiotics Research Institute under Reg. No. 1867.

Abstract: An isolated nucleic acid molecule encoding human skeletal muscle-specific ubiquitin-conjugating enzyme and comprising a nucleotide sequence coding for the amino acid sequence shown in SEQ ID NO:22 is disclosed. The isolation of this molecule makes it possible to detect its expression in various tissues, analyze its structure and function, and produce the human proteins encoded by this molecule by the technology of genetic engineering. In this way, it is possible to analyze the corresponding expression products, elucidate the pathology of diseases associated with the molecule, for example hereditary diseases and cancer, and diagnose and treat such diseases.

Abstract: A method for in vitro mutagenesis and recombination of polynucleotide sequences based on polymerase-catalyzed extension of primer oligonucleotides is disclosed. The method involves priming template polynucleotide(s) with random-sequences or defined-sequence primers to generate a pool of short DNA fragments with a low level of point mutations. The DNA fragments are subjected to denaturization followed by annealing and further enzyme-catalyzed DNA polymerization. This procedure is repeated a sufficient number of times to produce full-length genes which comprise mutants of the original template polynucleotides. These genes can be further amplified by the polymerase chain reaction and cloned into a vector for expression of the encoded proteins.

Abstract: This invention provides methods and chemical agents for enhancing transient expression in eukaryotic cells. Also provided are a model system for achieving prolonged transient expression in solid tumors, a means for culturing hepatocytes without feeder cells or an extracellular matrix bonded to the substratum, a method for manipulating cellular metabolism to reduce the consumption of glucose and a means for inducing the secretion of an endogenous phosphatase activity.