Abstract: The invention describes catalytic nucleic acid based compounds capable of cleaving nucleic acid polymers both in vivo and in vitro. Two embodiments of this invention are compounds with a short stem that does not base pair, a minizyme, and compounds with DNA hybridizing arms and RNA catalytic domain and stem, DNA-armed ribozymes. The compounds of this invention, while nucleotide based may be substituted or modified in the sugar, phosphate, or base. Methods of use and methods of treatment are also described.

Abstract: 2′-deoxy-2′-alkylnucleotides useful for stabilizing enzymatic nucleic acid molecules and antisense molecules.

Abstract: Nucleic acid molecule which modulates the synthesis, expression and/or stability of an mRNA encoding one or more receptors of vascular endothelial growth factor.

Abstract: Enzymatic nucleic acid molecules which modulate the expression and/or replication of hepatitis C virus (HCV).

Abstract: Vectors and a method for the identification of affector RNA molecules, such as ribozymes, external guide sequences, anti-sense RNA, and triple helix-forming RNA, that inhibit expression of target RNA molecules are disclosed. The method identifies functional affector RNA molecules by screening or selecting for those RNA molecules that inhibit expression of a fusion transcript, which includes the sequence of an RNA molecule of interest, from a library of potential affector RNA molecules. The vectors include a reporter gene encoding the fusion transcript including the RNA molecule of interest and RNA encoding the reporter protein. The vectors also include a second reporter gene encoding a second reporter protein. Expression of the second reporter protein can be used both to detect transformation or transfection of the vector into cells and as a control for effects on the expression of the first reporter protein that are not due to inhibition of expression of the RNA molecule of interest.

Abstract: The present invention discloses deoxyribonucleic acid enzymes—catalytic or enzymatic DNA molecules—capable of cleaving nucleic acid sequences or molecules, particularly RNA, in a site-specific manner, as well as compositions including same. Methods of making and using the disclosed enzymes and compositions are also disclosed.

Abstract: Nucleic acids comprising the RNA component of a mammalian telomerase are useful as pharmaceutical, therapeutic, and diagnostic reagents.

Abstract: Methods, employing a nucleotide integrase, for cleaving single-stranded RNA substrates, single-stranded DNA substrates, and double-stranded DNA substrates at specific sites and for inserting a nucleic acid molecule into the cleaved substrate are provided. One method uses a nucleotide integrase to cleave one strand of a double-stranded DNA substrate. The method comprises the steps of: providing an isolated nucleotide integrase comprising a group II intron RNA having two hybridizing sequences for hybridizing with two intron RNA binding sequences on the top strand of the DNA substrate, and a group II-intron encoded protein which binds to a first sequence element of the substrate; and reacting the nucleotide integrase with the double-stranded DNA substrate to permit the nucleotide integrase to cleave the top strand of the DNA substrate and to insert the group II intron RNA into the cleavage site.

Abstract: Method for one-pot deprotection of RNA molecules.

Abstract: VEGF (vascular endothelial growth factor) is a key regulator of angiogenesis, and agents that selectively decrease the VEGF levels may be used to treat malignancies and other angiogenic diseases characterized by high degree of vascularization or vascular permeability. A short oligonucleotide, or a derivative thereof, which has a sequence that corresponds to a particular part of a nucleic acid sequence which encodes VEGF, and which has a maximum length of 15 nucleotides, selectively inhibits VEGF expression. The invention further relates to a method of making the oligonucleotide and the use thereof.

Abstract: The present invention relates generally to a method for the prophylaxis and/or treatment of skin disorders, and in particular proliferative and/or inflammatory skin disorders, and to genetic molecules useful for same. The present invention is particularly directed to genetic molecules capable of modulating growth factor interaction with its receptor on epidermal keratinocytes to inhibit, reduce or otherwise decrease stimulation of this layer of cells. The present invention contemplates, in a most preferred embodiment, a method for the prophylaxis and/or treatment of psoriasis.

Abstract: The molecules and methods of the present invention provide a means for in vivo production of a trans-spliced molecule in a selected subset of cells. The pre-trans-splicing molecules of the invention are substrates for a trans-splicing reaction between the pre-trans-splicing molecules and a pre-mRNA which is uniquely expressed in the specific target cells. The in vivo trans-splicing reaction provides a novel mRNA which is functional as mRNA or encodes a protein to be expressed in the target cells. The expression product of the mRNA is a protein of therapeutic value to the cell or host organism a toxin which causes killing of the specific cells or a novel protein not normally present in such cells. The invention further provides PTMs that have been genetically engineered for the identification of exon/intron boundaries of pre-mRNA molecules using an exon tagging method.

Abstract: This invention is directed to improved catalytic compounds, minizymes and miniribozymes, capable of hybridizing with a target RNA to be cleaved. The minizymes and miniribozymes and compositions of the present invention may be used in vitro or in vivo. They may be used as diagnostic or therapeutic agents.

Abstract: The invention relates to a nucleic acid sequence, called “polyribozyme”, which has an endoribonuclease activity and is capable of inactivating the gene for the capsid protein of a virus, characterized in that it comprises: i) a sequence complementary to at least a part of the gene or its transcript or to its replication intermediates and, includes at distinct sites in this complementary sequence: ii) a plurality of ribozyme catalytic regions; iii) and, optionally, one or more sequences non-complementary to the transcript of the said gene, the said non-complementary sequence(s) being inserted between two consecutive bases of the complementary sequence.

Abstract: Method to produce a more active ribozyme by introducing a modified base into a substrate binding arm of the ribozyme or its catalytic core.

Abstract: Increased expression of a secreted FGF-binding protein (FGF-BP) occurs in certain autoimmune and malignant disease conditions. It is found, for example, that tumor secretions of FGF-BP results in mobilization and activation of locally-stored FGFs that can serve as an angiogenic switch molecule. Furthermore, it has been found that in an animal model of multiple sclerosis (MS), the exacerbation of the disease is accompanied by increased FGF-BP. Using ribozymes, it is possible to cause cleavage of the FGF-BP mRNA. Hence, administration of ribozymes which cleave the FGF-BP mRNA in sufficient amounts to inhibit disease processes triggered by FGF-BP is appropriate.

Abstract: This invention is directed to a compound having the formula: as defined in the detailed description. The compound may be covalently linked to a delivery agent. The invention also includes a composition which comprises the compound in association with an acceptable carrier. The invention also includes a method of cleaving an RNA target sequence which comprises contacting a target sequence with the compound as described above. Further, a method of treating a disease in man or animals associated with a particular RNA which comprises administrating to the man or animal the compound. Further, the invention also includes a diagnostic reagent which comprises the compound.

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: A synthetic RNA catalyst capable of cleaving an RNA substrate, the catalyst comprising a substrate binding portion and a “hairpin” portion. The invention also provides an engineered DNA molecule and a vector, each comprising a DNA sequence coding for an RNA catalyst according to the invention. The invention further comprises host cells transformed with the vectors of the invention which are capable of expressing the RNA catalyst. Finally, the invention provides a method of cleaving an RNA substrate which comprises contacting the substrate with a synthetic RNA catalyst according to the invention.

Abstract: The present invention concerns a method for detecting the presence of a catalytically active ribozyme in a medium. The detection of the catalytically active ribozyme may be a goal by itself, or the ribozyme may serve as a reporter for the presence of other biomolecules in an assayed sample. The detection is carried out in a catalytic system wherein the presence of the active ribozyme serves to produce other active ribozymes in a positive-feedback amplificatory manner.

Abstract: The invention relates to an ionic conjugate, which is stable in a biological medium, and which is comprised of a particle vector with at least one cationic, nonliquid, hydrophilic nucleus and of polyanionic oligonucleotides. The invention further concerns the pharmaceutical compositions containing these conjugates and the use of a particle vector to carry the oligonucleotides to the cells.

Abstract: Circular RNAs may be synthesized by inserting DNA fragments into a plasmid containing sequences having the capability of spontaneous cleavage and self-circularization. Insertion of the DNA fragments allows RNAs of predetermined size to be constructed. In addition, a two-dimensional polyacrylamide gel electrophoresis system having a second dimension more highly cross-linked than the first dimension permits the separation and analysis as well as the precise sizing of both linear and circular RNAs produced by the synthetic method.

Abstract: The present invention provides methods for increasing ribozyme catalytic activity without reducing specificity, which methods comprise contacting an RNA molecule with a ribozyme having a flanking sequence modified to contain 2′-O-substituted nucleotides. The invention also provides ribozymes comprising a flanking sequence modified to contain 2′-O-substituted nucleotides. In addition, the invention provides methods for increasing ribozyme catalytic activity comprising contacting an RNA molecule with a ribozyme having a flanking sequence modified to contain a 2′-O-substituted nucleotide and a facilitator oligonucleotide. The present invention further provides compositions comprising a ribozyme having modified flanking sequences and an effective amount of a facilitator oligonucleotide.

Abstract: The present invention provides a method of inhibiting the proliferation of cells. The method comprises inhibiting induction or decreasing expression of Egr-1 or decreasing the nuclear accumulation or activity of the Egr-1 gene product. The present invention also provides a method of reducing the incidence of restenosis in a subject. The method comprises administering to the subject an agent which inhibits induction or decreases expression of Egr-1 or decreases the nuclear accumulation or activity of the Egr-1 gene product.

Abstract: The present invention relates to genes in Saccharomyces cerevisiae which are essential for germination and proliferation of S. cerevisiae and using the identified genes or their encoded proteins as targets for highly specific antifungal agents, insecticides, herbicides and anti-proliferation drugs. The present invention provides antisense molecules and ribozymes comprising sequences complementary to the sequences of mRNAs of essential genes that function to inhibit the essential genes. The present invention also provides neutralizing antibodies to proteins encoded by essential genes that bind to and inactivate the essential gene products. The present invention further provides pharmaceutical compositions for treating fungal and proliferative diseases, as well as methods of treatment of fungal and proliferative diseases.

Abstract: The present invention discloses nucleic acid enzymes capable of cleaving single-stranded DNA in a site specific manner.

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: 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: 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: The invention is an expression cassette for the antisense expression of ribozyme, having a strong promotor, suitably a T7 promotor, an adenoviral va-RNA gene, a stable loop region, and an insertion site for the antisense/ribozyme sequence in the loop region.