Abstract: Hepatitis delta is used as a vector for inhibition of viral infection and to express proteins in vivo in a cell-specific manner. The scope of delta's use as a vector is broadened in the present invention in several important ways. For example, a delta RNA genome capable of self-replication is enlarged to carry additional information, either coding for messenger RNA for a protein, or for a targeted ribozyme, which can be delivered to liver cells using delta's normally infectious properties, or to other cell types using chimeric delta viral agents carrying altered surface proteins. In another embodiment, the delta vector is made self-limiting, so that its role in delivering targeted information is separated from its viral property of unlimited infectious replication. Targeting is achieved through the use of sequences flanking the delta sequences that have affinity for sites on RNA to be cleaved.

Abstract: The present invention is directed to nucleic acid molecules encoding a truncated human cyclin E protein, the truncated human cyclin E protein being a constitutively active form of human cyclin E protein. These truncated forms can be encoded by the nucleotide sequence of wild-type cyclin E, with a deletion therein to result in the truncated protein. Vectors and host cells containing the nucleic acid molecules are also provided. The invention further provides isolated fragments of the truncated cyclin E proteins, which fragments consist essentially of the deletion flanking regions of the wild-type cyclin E nucleotide sequence. Antisense nucleic acid molecules, and fragments thereof, to the truncated cyclin E protein and to the fragments thereof are also provided. Methods using the nucleic acid molecules, fragments thereof, antisense nucleic acid molecules, and fragments thereof, are provided. The antisense can be used therapeutically for inhibition of cyclin E activity.

Abstract: Lipid molecules bearing a cationic charge are described. These cationic lipids are useful in the delivery of biomolecules, such as oligonucleotides, nucleic acids, peptides, diagnostic imaging agents, proteins and drug molecules. In the form of liposomes, they can effectively be used for the intracellular delivery of biomolecules for therapeutic or diagnostic purposes.

Abstract: This invention relates to delivery of biologically active cargo molecules, such as polypeptides and nucleic acids, into the cytoplasm and nuclei of cells in vitro and in vivo. Intracellular delivery of cargo molecules according to this invention is accomplished by the use of novel transport polypeptides which comprise HIV tat protein or one or more portions thereof, and which are covalently attached to cargo molecules. The transport polypeptides in preferred embodiments of this invention are characterized by the presence of the tat basic region (amino acids 49-57), the absence of the tat cysteine-rich region (amino acids 22-36) and the absence of the tat exon 2-encoded carboxy-terminal domain (amino acids 73-86) of the naturally-occurring tat protein. By virtue of the absence of the cysteine-rich region, the preferred transport polypeptides of this invention solve the potential problems of spurious trans-activation and disulfide aggregation.

Abstract: Oligonucleotides are provided which are targeted to nucleic acids encoding human c-raf and capable of inhibiting raf expression. The oligonucleotides contain a methoxyethoxy (2'-O--CH.sub.2 CH.sub.2 OCH.sub.3) modification at the 2' position of at least one nucleotide. Methods of inhibiting the expression of human raf using oligonucleotides of the invention are also provided. The present invention further comprises methods of inhibiting hyperproliferation of cells and methods of treating abnormal proliferative conditions which employ oligonucleotides of the invention.

Abstract: The present invention concerns the use of oligonucleotides to inhibit propagation of human immunodeficiency virus (HIV). Preferred HIV target sites are identified and oligonucleotides designed to hybridize to a target site, or be analogous to a target site, are described. The preferred use of the oligonucleotides is to inhibit HIV propagation in a patient infected with HIV.

Abstract: A compound consisting essentially of polylysine conjugated to non-charged residues and recognition signals wherein the free amino functions of said polylysine are substituted with non-charged residues and said recognition signals, which non-charged residues consist of gluconalactone and which recognition signals are at least one member of the group consisting of galactoside, mannoside, fucoside, Lewis.sup.x, Lewis.sup.b, oligomannoside, oligolactosamine saccharides and peptide ANP and said conjugated polylysine contains at least 30% unsubstituted free amino functions and a method of transfecting cultured cells.

Abstract: Covalent cross-linkages for two oligonucleotide strands or for first and second regions of a single oligonucleotide strand connect sugar moieties of nucleotides on the respective strands or the regions of the single strand. The cross-linkages are connected to at least one strand or region via a space-spanning group. The cross-linkage also can be connected to the other strand or other region via a space-spanning group or via an abasic site located on the other strand or other region.

Abstract: The present invention relates to methods of treating disease-associated cellular proliferation using oligonucleotides. In particular, it relates to the use of oligonulceotides which are substantially complementary to interleukin-6 receptor mRNA sequences. In the form of pharmaceutical compositions, these oligonucleotides are suitable for administration to human subjects for the treatment of abnormal cellular proliferation due to such diseases as cancer, autoimmune disorders and viral infection.

Abstract: Compounds having highly specific endoribonuclease activity are described. The compounds of this invention, also known as ribozymes, comprise ribonucleotides having two hybridizing regions with predetermined sequences capable of hybridizing with a plant, animal or viral target RNA, a region of defined sequence and a base paired stem region.

Abstract: Protein disulfide isomerase, which catalyzes the exchange reaction between sulfhydryl and disulfide in a protein for formation of the most stable natural type disulfide bonds, is useful for formation of natural type disulfide bonds in a protein which is produced in a prokaryotic cell.

Abstract: The peptide X-Arg-Gly-Asp-R-Y wherein X is H or at least one amino acid and Y is OH or at least one amino acid, and R is an amino acid selected from Thr or Cys, or other amino acid, having the same cell-attachment activity as fibronectin and the peptide X-Arg-Gly-Asp-Ser-Y, wherein X and Y, having said activity are disclosed.

Abstract: Tetrahydrofuranyl compounds are provided that are functionalized to include pendant conjugate groups, and which are useful in diagnostic assays and as research reagents. Novel intermediates for the synthesis of the compounds are also provided.

Abstract: The invention concerns a method for creating, identifying, and isolating ribozymes capable of binding a selected ligand and catalyzing a reaction involving the selected ligand. The method entails sequential selections for ligand binding molecules and catalytic molecules. The invention also includes novel ribozymes produced by these methods.

Abstract: Method and compositions for increasing telomere length in normal cells can be used to increase the proliferative capacity of cells and to delay the onset of cellular senescence.

Abstract: Disclosed are ribozyme analogs having the ability to endonucleolytically cleave a sequence of 3' to 5' linked ribonucleotides. The ribozyme analogs include a plurality of 3' to 5' covalently-linked nucleotides, and a rigid molecular linker having at least one non-nucleotidic molecule covalently linked to two of the nucleotides. Also disclosed are methods of preparing and utilizing the ribozyme analogs of the invention, and pharmaceutical formulations and kits containing such ribozyme analogs.

Abstract: Oligonucleotide-mimicking macromolecules that have improved nuclease resistance are provided. Replacement of the normal phosphorodiester inter-sugar linkages found in natural oligonucleotides with four atom linking groups provide unique compounds that are useful in regulating RNA expression and in therapeutics. Methods of synthesis and use also are disclosed.

Abstract: This invention relates to delivery of biologically active cargo molecules, such as polypeptides and nucleic acids, into the cytoplasm and nuclei of cells in vitro and in vivo. Intracellular delivery of cargo molecules according to this invention is accomplished by the use of novel transport polypeptides which comprise HIV tat protein or one or more portions thereof, and which are covalently attached to cargo molecules. The transport polypeptides in preferred embodiments of this invention are characterized by the presence of the tat basic region (amino acids 49-57), the absence of the tat cysteine-rich region (amino acids 22-36) and the absence of the tat exon 2-encoded carboxy-terminal domain (amino acids 73-86) of the naturally-occurring tat protein. By virtue of the absence of the cysteine-rich region, the preferred transport polypeptides of this invention solve the potential problems of spurious trans-activation and disulfide aggregation.

Abstract: The present invention provides stem-loop and circular oligonucleotides each with at least one Watson-Crick binding (WC) domain and at least one corresponding Hoogsteen binding (H) domain separated from each other by linker domains. Each WC domain has sufficient complementarity to bind to one strand of a defined nucleic acid target by Watson-Crick base pairing in an anti-parallel orientation. Each corresponding H domain is capable of binding to the WC domain by Hoogsteen base pairing in an anti-parallel manner. The present invention also provides methods of making and using these oligonucleotides as well as kits and pharmaceutical compositions containing these oligonucleotides.

Abstract: This invention relates to a novel nucleic acid sequence encoding a novel human phosphodiesterase IV (hPDE IV) isozyme. It also relates to a polypeptide encoded by such sequence.This invention also relates to an assay method for detecting the presence of such novel isozyme in human cells, and to a method of identifying compounds or other substances that inhibit or modify the activity of such isozyme.