Abstract: The present invention relates to a method of determining predisposition to low or high bone mineral density and to development of osteoporosis of a patient, which comprises determining estrogen receptor polymorphism in linkage disequilibrium in a biological sample of said patient, wherein heterozygosity is associated with high bone density and homozygosity is associated with low bone density.

Abstract: The present invention provides novel human genes, for example a novel human gene comprising a nucleotide sequence coding for the amino acid sequence shown under SEQ ID NO:1. The use of the genes makes it possible to detect the expression of the same in various tissues, analyze their structures and functions, and produce the human proteins encoded by the genes by the technology of genetic engineering. Through these, it becomes possible to analyze the corresponding expression products, elucidate the pathology of diseases associated with the genes, for example hereditary diseases and cancer, and diagnose and treat such diseases.

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: Novel oligomers are disclosed which have enhanced ability with respect to forming duplexes or triplexes compared with oligomers containing only conventional bases. The oligomers contain the bases 5-(1-propynyl)uracil, 5-(1-propynyl)cytosine or related analogs. The oligomers of the invention are capable of (i) forming triplexes with various target sequences such as virus or oncogene sequences by coupling into the major groove of a target DNA duplex at physiological pH or (ii) forming duplexes by binding to single-stranded DNA or to RNA encoded by target genes. The oligomers of the invention can be incorporated into pharmaceutically acceptable carriers and can be constructed to have any desired sequence, provided the sequence normally includes one or more bases that is replaced with the analogs of the invention.

Abstract: The invention provides tissue-specific and target RNA-specific ribozymes. These ribozymes can be used to destroy target-specific neoplasms and to treat viral infections, among other uses. The ribozymes of the present invention comprise a 5' autocatalytically cleaving ribozyme sequence, a catalytic ribozyme comprising a target RNA-specific binding site and a 3' autocatalytically cleaving ribozyme. The invention also provides nucleic acids which encode the ribozymes of the invention. These nucleic acids can be used to express the ribozymes of the invention at the selected site. Methods of treating disease by administering the ribozymes are provided.

Abstract: The present invention relates to a radiolabeled DNA oligonucleotide, a method of preparation thereof and the therapeutic uses of this substance to prevent uncontrolled cellular proliferation. The invention also relates to devices incorporating the above radiolabeled DNA oligonucleotide for the therapeutic treatment of uncontrolled cellular proliferation. More specifically, the present invention is concerned with the prevention of restenosis by coronary delivery of radiolabeled DNA oligonucleotide at a dilatation site of an artery. This invention is also directed to a method of treatment of vascular proliferative diseases and/or other proliferative disorders such as cancer and related metastasis.

Abstract: The inhibition of proteins synthesis by an antisense RNA-tRNA complex which is capable of inhibiting translation is described. Under certain conditions, growth of organisms is inhibited by inhibition of non-specific translation by an antisense RNA construct to a tRNA target. In vitro, cell-free inhibition of viral protein translation is described. Transformed microorganisms are disclosed. The invention has applicability in the control of cell growth, such as viruses, bacteria, infected cells, or tumor cells. The invention is useful in animal and plant fields.

Abstract: A C-terminal .alpha.-amidating enzyme of Xenopus laevis and precursor thereof produced by a recombinant DNA technique; a DNA coding for the enzyme or precursor thereof; a plasmid containing the DNA; a host organism transformed with the plasmid; a process for production of the enzyme using the transformant; and a process for production of a C-terminal .alpha.-amidated peptide using the enzyme.

Abstract: The present invention provides stem-loop oligonucleotides containing a double-stranded stem domain of at least about 2 base pairs and a single-stranded loop domain. The loop domains of the present oligonucleotides include at least one parallel binding (P) domain separated by at least about 3 nucleotides from a corresponding anti-parallel binding (AP) domain. Each P and corresponding AP domain of the present oligonucleotides can bind detectably to one strand of a defined nucleic acid target wherein the P domain binds in a parallel manner to the target and the corresponding AP domain binds in an anti-parallel manner to the target. The present stem-loop oligonucleotides can bind to both single-stranded and double-stranded target nucleic acids. The present invention also provides methods of using these oligonucleotides as well as kits and pharmaceutical compositions containing these oligonucleotides.

Abstract: A recombinant RNA virus is provided allowing encapsidation of genetically engineered viral sequences in heterologous, preferably rod-shaped coat, protein capsids. Since icosahedral viruses are limited in the amount of RNA they can carry, and rod-shaped viruses are expansible, this invention allows the size of recombinant virus RNA components to be increased (or decreased). Methods of making and using such recombinant viruses are also provided, specifically with respect to the transfection of plants to bring about genotypic and phenotypic changes.

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: Recombinant nucleic acids which encode aminoacyl-tRNA sythetases of helicobacter origin have been isolated. These nucleic acids can be used to make expression constructs and transformed host cells for the production of helicobacter aminoacyl-tRNA synthetases. They can also be used in the further isolation of nucleic acids related by DNA sequence similarities, which also encode helicobacter aminoacyl-tRNA synthetases, or portions thereof. A further embodiment of the invention is antisense nucleic acid which can hybridize to the nucleic acid which encodes the aminoacyl-tRNA synthetase of helicobacter. The invention also relates to isolated and/or recombinant helicobacter aminoacyl-tRNA synthetases. Antibodies which bind to these enzymes can be made and can be used in the purification and study of the enzymes.

Abstract: Disclosed are synthetic oligonucleotides 15 to 50 nucleotides in length which are specifically hybridizable with at least a portion of RNA or DNA derived from the UL36, UL84, UL101x-102, or UL112-113 genes of a cytomegalovirus. Also disclosed are pharmaceutical compositions including an oligonucleotide of the invention and methods of inhibiting cytomegalovirus infection using such oligonucleotides.

Abstract: Oligonucleotide signalling conjugates including a nucleic acid sequence, an amino-group containing linker group, a sulphur (thio) containing group and a non-isotopic label or marker and thiolated oligonucleotide derivative intermediates reactive with activated non-isotopic label or marker are described. The non-isotopic label is especially an enzyme such as alkaline phosphatase or horse radish peroxidase. The conjugates have application in the detection or characterisation of nucleic acid sequences and in particular in genetic characterisation.

Abstract: Amplification and sequencing of a selected region of a target nucleic acid polymer are be performed in a single vessel. The sample is added to an amplification mixture containing a thermally stable polymerase and nucleoside feedstocks. Chain terminating dideoxynucleosides are added either at the beginning of the amplification reaction or during the course of the amplification. A thermally stable polymerase which incorporates dideoxynucleotides into an extending oligonucleotide at a rate which is no less than about 0.4 times the rate of incorporation of deoxynucleosides can be used in the amplification mixture or added with the chain terminating nucleoside.

Abstract: An enzymatic nucleic acid molecule, comprising a moiety having the formula: ##STR1## wherein B is a nucleotide base or hydrogen; R is selected from the group consisting of aminoacyl group, and NHR.sub.4 group, wherein said R.sub.4 is independently selected from the group consisting of a peptidyl group containing between 2 and 5 amino acids inclusive, and CO--CR.sub.1 R.sub.2 R.sub.3, wherein R.sub.1, R.sub.2 and R.sub.3 independently is selected from the group consisting of hydrogen, an alkyl group containing between 2 and 10 carbon atoms inclusive, and an alkyl amine; and the zigzag lines are independently hydrogen or a bond.

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

Abstract: A prototype RNA cyclase ribozyme that allows efficient production of circular RNA. Methods for modifying the prototype to produce a wide variety of custom circular RNA are detailed. The method utilizes a new plasmid which enables production of a wide variety of imaginable RNA sequences in a covalent, circular form free from intron sequences in vitro. At a particular site in the plasmid, a sequence coding for the desired circular RNA is inserted to create a new RNA cyclase ribozyme gene. RNA transcribed from RNA cyclase ribozyme genes autocatalytically converts the desired RNA sequence it contains into circular form. RNA cyclase genes may be placed into appropriate expression vectors for synthesis of circular RNA in vivo as part of ribozyme or antisense gene regulation approaches to genetic engineering.

Abstract: Antimicrobial proteins capable of isolation from seeds of Allium show a wide range of antifungal activity and some activity against Gram-positive bacteria. DNA encoding the proteins may be isolated and incorporated into vectors. Plants transformed with this DNA may be produced. The proteins find commercial application as antifungal or antibacterial agents; transformed plants will show increased disease resistance.

Abstract: A eukaryotic, global negative regulator of class II transcription, DNA sequences encoding the negative regulator and results demonstrating the activity of the purified negative regulator protein to repress class II transcription are described.