Abstract: A method, composition and kit for synthesizing multiple copies of a target nucleic acid sequence autocatalytically under conditions of substantially constant temperature, ionic strength, and pH are provided in which multiple RNA copies of the target sequence autocatalytically generate additional copies using a mixture of blocked and unblocked primers and/or promoter-primers to initiate DNA and RNA synthesis, preferably with reduced non-specific product formation. The invention is useful for generating copies of a nucleic acid target sequence for purposes that include assays to quantitate specific nucleic acid sequences in clinical, environmental, forensic and similar samples, cloning and generating probes.

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: 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: 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 gp13O 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: The present invention relates to methods of synthesizing phosphorothioate oligonucleotides. In particular, it relates to the use of certain restriction endonucleases to cleave phosphorothioate oligonucleotides which contain restriction endonuclease recognition sequences. These restriction sequences facilitate the cleavage of relatively cleavage resistant phosphorothioate oligonucleotides thus facilitating their separation and purification after synthesis.

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: The invention features the use of a purified first targeted oligonucleotide in combination with either 1) a subtargeted oligonucleotide, 2) second targeted oligonucleotide, or 3) a non-targeted phosphorothioate oligonucleotide, to inhibit protein production of a targeted nucleic acid sequence, cell proliferation, and/or the multiplication of a foreign organism. The subtargeted oligonucleotide contains a truncated version of the targeted oligonucleotide.

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: 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: The present invention relates to oligonucleotides which are effective inhibitors of disease-associated cellular proliferation. In particular, it relates to the use of oligonulceotides which are substantially complementary to gp130 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: The present invention relates to methods of cleaving phosphorothioate oligonucleotides. In particular, it relates to the use of certain restriction endonucleases to cleave phosphorothioate oligonucleotides which contain restriction endonuclease recognition sequences. These restriction sequences can be used to facilitate the cleavage of relatively cleavage resistant phosphorothioate oligonucleotides thus facilitating their separation and purification after synthesis.

Abstract: Method for destroying the ability of a nucleic acid to be amplified, comprising the step of contacting the nucleic acid with bleach in an amount and for a time sufficient to inhibit the ability of that nucleic acid to be amplified in an amplification reaction.

Abstract: A fluorescent label compound having the formulaA--B.sup.1 --B.sup.2 --B.sup.3 --CwhereinA represents the residue of a natural or synthetic nucleotide or nucleoside or a derivative thereof;B.sup.1 represents a divalent spacer radical or a single bond;B.sup.2 represents a divalent spacer radical;B.sup.3 represents a divalent spacer radical or a single bond; andC represents a coumarin radical having the formula ##STR1## in which R.sup.1 represents hydrogen or cyano;R.sup.2 represents phenyl or thiazolyl bonded in the 2-, 4- or 5-position, wherein the phenyl is unsubstituted or substituted by nitro, cyano, amino, --NH--C.sub.1-4 -alkyl, --(CH.sub.2).sub.1-4 --NH.sub.2, --(CH.sub.2).sub.1-4 --NH--(CH.sub.2).sub.1-3 --CH.sub.3, carboxy, C.sub.1-4 -alkoxycarbonyl, C.sub.1-4 -alkoxycarbonyloxy, hydroxy, C.sub.1-4 -alkylaminocarbonyl, or C.sub.1-4 -alkylcarbonylamino and either further unsubstituted or substituted by C.sub.

Abstract: A method, composition and kit for amplifying a target nucleic acid sequence under conditions of substantially constant temperature, ionic strength, and pH and using only a single promoter-primer. To effect the amplification, a supply of a single promoter-primer having a promoter and a primer complementary to the 3'-end of the target sequence, and a reverse transcriptase and an RNA polymerase are provided to a mixture including the target sequence; the amplification proceeds accordingly. The invention is useful for generating copies of a nucleic acid target sequence for purposes that include assays to quantitate specific nucleic acid sequences in clinical, environmental, forensic and similar samples, cloning and generating probes.

Abstract: A method for detecting (i) one or more microorganisms or (ii) nucleic acid sequences from a prokaryotic source or an eukaroytic source in an unpurified nucleic acid-containing test sample comprising(a) labeling the nucleic acids in the test sample,(b) contacting, under hybridization conditions, the labeled hybridizable nucleic acid and one or more immobilized hybridizable nucleic acid probes comprising (i) one or more known microorganisms or (ii) sequences from eukaroytic or prokaryotic sources, to form hybridized labeled nucleic acids, and(d) assaying for the hybridized nucleic acids by detecting the label. The method can be used to detect genetic disorders, e.g., sickle-cell anemia.

Abstract: A process for detecting a nucleic acid sequence in a sample comprising:(1) treating said sample under hybridization conditions with an oligonucleotide that lacks a recognition site for enzyme digestion;(2) extending the hybridization product from step (1) by adding polymerase and NTPs to create on the oligonucleotide strand a recognition site for enzyme digestion;(3) treating the product of step (2) with labeled probe, which is immobilized or immobilizable and which contains a recognition site for enzyme digestion that is completely or partially complementary to the recognition site for enzyme digestion on the oligonucleotide strand, under conditions that the oligonucleotide strand becomes hybridized to the labeled probe;(4) digesting the separated hybridization product of step (3) with restriction endonuclease; and(5) detecting the separated label which is released in solution.

Abstract: Specific nucleic acid sequences are amplified through the use of a hairpin probe which, upon hybridization with and ligation to, a target sequence is capable of being transcribed. The probe comprises a single stranded self-complementary sequence which, under hybridizing conditions, forms a hairpin structure having a functional promoter region, and further comprises a single stranded probe sequence extending from the 3' end of the hairpin sequence. Upon hybridization with a target sequence complementary to the probe sequence and ligation of the 3' end of the hybridized target sequence to the 5' end of the hairpin probe, the target sequence is rendered transcribable in the presence of a suitable RNA polymerase and appropriate ribonucleoside triphosphate (rNTPs).

Abstract: A photochemical nucleic acid-labeling reagent of the formula ##STR1## wherein Q is a photoreactive residue of a nucleic acid-binding ligand; L is a detectable label residue; R is hydrogen, C.sub.1 to C.sub.7 -alkyl, aryl, hydroxy, or C.sub.1 to C.sub.7 -alkoxy; x is an integer from 2 through 7; and Y is an integer from 3 through 10; wherein R and x, respectively, can be the same or different each time they appear in the formula. The reagent is useful in the highly efficient labeling of nucleic acids for the purpose of detection in hybridization assays.

Abstract: A process for determining the presence of a particular nucleic acid sequence in a test sample comprising(a) chemically modifying nucleic acids in the test sample either to introduce a label or a reactive site in a manner that supports their hybridizability,(b) contacting under hybridization conditions the chemically modified sample nucleic acids with a hybridizable nucleic acid probe which either, when the sample nucleic acids have been modified to introduce a label, carrys a reactive site or, when the sample nucleic acids have been modified to introduce a reactive site, is labeled,(c) contacting the solution resulting from step (b) with a immobilized form of a reactive partner to the reactive site to form a stable bond with the reactive site on the sample nucleic acids or the probe, respectively,(d) separating the resulting immobilized fraction from the remaining solution, and(e) determining the presence of the label in the separated immobilized fraction or a decrease in the label in the remaining solution.

Abstract: A labeled nucleic acid probe comprising (a) a nucleic acid component, (b) a nucleic acid-binding ligand photochemically linked to the nucleic acid component, and (c) a label chemically linked to the nucleic acid-binding ligand. The label can be a specifically bindable ligand such as a hapten or biotin, an enzyme such as a .beta.-galactosidase or horse radish peroxidase, a fluorescent radical, a phycobiliprotein, a luminescent radical, or a radioisotope. The probe can be used in assays of nucleic acids, taking advantage of the ability of the nucleic acid component to hydridize.