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258 results about "Nucleobase" patented technology

Nucleobases, also known as nitrogenous bases or often simply bases, are nitrogen-containing biological compounds that form nucleosides, which in turn are components of nucleotides, with all of these monomers constituting the basic building blocks of nucleic acids. The ability of nucleobases to form base pairs and to stack one upon another leads directly to long-chain helical structures such as ribonucleic acid (RNA) and deoxyribonucleic acid (DNA).

Xylo-LNA analogues

Based on the above and on the remarkable properties of the 2′-O,4′-C-methylene bridged LNA monomers it was decided to synthesise oligonucleotides comprising one or more 2′-O,4′-C-methylene-β-D-xylofuranosyl nucleotide monomer(s) as the first stereoisomer of LNA modified oligonucleotides. Modelling clearly indicated the xylo-LNA monomers to be locked in an N-type furanose conformation. Whereas the parent 2′-deoxy-β-D-xylofuranosyl nucleosides were shown to adopt mainly an N-type furanose conformation, the furanose ring of the 2′-deoxy-β-D-xylofuranosyl monomers present in xylo-DNA were shown by conformational analysis and computer modelling to prefer an S-type conformation thereby minimising steric repulsion between the nucleobase and the 3′-O-phopshate group (Seela, F.; Wömer, Rosemeyer, H. Helv. Chem. Acta 1994, 77, 883). As no report on the hybridisation properties and binding mode of xylo-configurated oligonucleotides in an RNA context was believed to exist, it was the aim to synthesise 2′-O,4′-C-methylene-β-D-xylofuranosyl nucleotide monomer and to study the thermal stability of oligonucleotides comprising this monomer. The results showed that fully modified or almost fully modified Xylo-LNA is useful for high-affinity targeting of complementary nucleic acids. When taking into consideration the inverted stereochemistry at C-3′ this is a surprising fact. It is likely that Xylo-LNA monomers, in a sequence context of Xylo-DNA monomers, should have an affinity-increasing effect.
Owner:QIAGEN GMBH

Oligonucleotides comprising a modified or non-natural nucleobase

One aspect of the present invention relates to a double-stranded oligonucleotide comprising at least one non-natural nucleobase. In certain embodiments, the non-natural nucleobase is difluorotolyl, nitroindolyl, nitropyrrolyl, or nitroimidazolyl. In a preferred embodiment, the non-natural nucleobase is difluorotolyl. In certain embodiments, only one of the two oligonucleotide strands comprising the double-stranded oligonucleotide contains a non-natural nucleobase. In certain embodiments, both of the oligonucleotide strands comprising the double-stranded oligonucleotide independently contain a non-natural nucleobase. In certain embodiments, the oligonucleotide strands comprise at least one modified sugar moiety. Another aspect of the present invention relates to a single-stranded oligonucleotide comprising at least one non-natural nucleobase. In a preferred embodiment, the non-natural nucleobase is difluorotolyl. In certain embodiments, the ribose sugar moiety that occurs naturally in nucleosides is replaced with a hexose sugar, polycyclic heteroalkyl ring, or cyclohexenyl group. In certain embodiments, at least one phosphate linkage in the oligonucleotide has been replaced with a phosphorothioate linkage.
Owner:ALNYLAM PHARM INC

Phosphinoamidite carboxylates and analogs thereof in the synthesis of oligonucleotides having reduced internucleotide charge

Nucleoside phosphinoamidite carboxylates and analogs are provided that have the structure of formula (III)wherein A is hydrogen, hydroxyl, lower alkoxy, lower alkoxy-substituted lower alkoxy, halogen, SH, NH2, azide or DL wherein D is O, S or NH and L is a heteroatom-protecting group, unsubstituted hydrocarbyl, substituted hydrocarbyl, heteroatom-containing hydrocarbyl, or substituted heteroatom-containing hydrocarbyl; B is a nucleobase; and one of R11 and R12 is a blocking group and the other is (IV) or (VI)in which W, X, Y, Z, R1 and n are as defined herein.
Owner:AGILENT TECH INC

Pharmaceutical Composition Comprising Anti-Mirna Antisense Oligonucleotides

ActiveUS20100286234A1Reduced microRNA levelAvoid off-target effectsOrganic active ingredientsSugar derivativesNucleobaseRNA Cleavage
The invention provides pharmaceutical compositions comprising short single stranded oligonucleotides, of length of between 8 and 26 nucleobases which are complementary to human microRNAs selected from the group consisting of miR19b, miR21, miR122a, miR155 and miR375. The short oligonucleotides are particularly effective at alleviating miRNA repression in vivo. It is found that the incorporation of high affinity nucleotide analogues into the oligonucleotides results in highly effective anti-microRNA molecules which appear to function via the formation of almost irreversible duplexes with the miRNA target, rather than RNA cleavage based mechanisms, such as mechanisms associated with RNaseH or RISC.
Owner:ROCHE INNOVATION CENT COPENHAGEN

Methods and compositions for the tandem synthesis of two or more oligonucleotides on the same solid support

The present invention relates to novel methods and novel solid support materials for the tandem synthesis of two or more different oligonucleotides on the same solid support in one synthetic run. The methods involve novel support preparations comprised of two or more types of orthogonally protected anchor groups. Subsequent to the selective removal of the first of the respective protective groups, the first oligonucleotide is assembled on the deblocked anchor groups according to standard methods, preferably via phosphoramidite chemistry. Following the capping of said first oligonucleotide, the anchor groups blocked by the second type of protective group are selectively liberated and serve is the starting point for the assembly of a second oligonucleotide, and so forth. After completion of all of the syntheses on the solid support, the oligonucleotides are released from the solid support and deprotected at the nucleobases, using standard methods. Preparations obtained using the method of this invention, generally contain two or more different oligonucleotides. Such preparations are particularly useful in applications that require pairs of oligonucleotide primers, several probes at a time, duplexed nucleic acid fragments, or other combinations of oligonucleotides that are useful in applications such as PCR, sequencing, multiplexed genotyping, cloning and RNA interference. The invention includes procedures for the preparation of the novel solid supports of the invention.
Owner:SIGMA ALDRICH CO LLC

Pseudonucleotide comprising an intercalator

The present invention relates to intercalator pseudonucleotides. Intercalator pseudonucleotides according to the invention are capable of being incorporated into the backbone of a nucleic acid or nucleic acid analogue and they comprise an intercalator comprising a flat conjugated system capable of co-stacking with nucleobases of DNA. The invention also relates to oligonucleotides or oligonucleotide analogues comprising at least one intercalator pseudo nucleotide. The invention furthermore relates to methods of synthesising intercalator pseudo nucleotides and methods of synthesising oligonucleotides or oligonucleotide analogues comprising at least one intercalator pseudonucleotide. In addtition, the invention describes methods of separating sequence specific DNA(s) from a mixture comprising nucleic acids, methods of detecting a sequence specific DNA (target DNA) in a mixture comprising nucleic acids and / or nucleic acid analogues and methods of detecting a sequence specific RNA in a mixture comprising nucleic acids and / or nucleic acid analogues. In particular said methods may involve the use of oligonucleotides comprising intercalator pseudo nucleotides. The invention furthermore relates to pairs of oligonucleotides or oligonucleotide analogues capable of hybridising to one another, wherein said pairs comprise at least one intercalator pseudonucleotide. Methods for inhibiting a DNAse and / or a RNAse and methods of modulating transcription of one or more specific genes are also described.
Owner:HUMAN GENETIC SIGNATURES PTY LTD

Nucleobase editors and uses thereof

Some aspects of this disclosure provide strategies, systems, reagents, methods, and kits that are useful for the targeted editing of nucleic acids, including editing a single site within the genome ofa cell or subject, e.g., within the human genome. In some embodiments, fusion proteins of Cas9 and nucleic acid editing proteins or protein domains, e.g., deaminase domains, are provided. In some embodiments, methods for targeted nucleic acid editing are provided. In some embodiments, reagents and kits for the generation of targeted nucleic acid editing proteins, e.g., fusion proteins of Cas9 andnucleic acid editing proteins or domains, are provided.
Owner:PRESIDENT & FELLOWS OF HARVARD COLLEGE

Alkylated hexitol nucleoside analogues and oligomers thereof

The present invention is directed to nucleoside analogues with as substitute for the sugar part a 1,5-anhydrohexitol moiety, doexygenated and substituted with a nucleobase at the 2-position, of which the hexitorl ring is further substituted with at least one alkoxy substituent at the 3-position or at the 1-position, and to oligonucleotides wherein at least some of the nucleotides are part of the afore mentioned hexitol nucleoside analogues and exhibit sequence-specific hydridization to complementary sequences of nucleic acids, and maintaining or improving the hybridisation strength. The invention further relates to nucleoside analogues with a 1,5-anhydrohexitol moiety as the sugar part, deoxygenated and substituted with a nucleobase at the 2-position, of which the hexitol ring is substituted with a methoxy substituent at the 1-position, having at the same time either a hydroxy or an alkoxy group at the 3-position, or having a 3-deoxygenated position. The inclusion of one or more of the afore mentioned hexitol nucleoside analogues in oligonucleotides provides, inter alia, either for improved binding or for maintained binding of these oligonucleotides to a complementary strand. This invention further relates to the chemical synthesis of these oligomers which are useful diagnostics, therapeutics and as research agents.
Owner:K U LEUVEN RES & DEV

Artificial promoter libraries for selected organisms and promoters derived from such libraries

An artificial promoter library (or a set of promoter sequences) for a selected organism or group of organisms is constructed as a mixture of double stranded DNA fragments, the sense strands of which comprise at least two consensus sequences of efficient promoters from said organism or group of organisms, or parts thereof comprising at least half of each, and surrounding intermediate nucleotide sequences (spacers) of variable length in which at least 7 nucleotides are selected randomly among the nucleobases A, T, C and G. The sense strands of the double stranded DNA fragments may also include a regulatory DNA sequence imparting a specific regulatory feature, such as activation by a change in the growth conditions, to the promoters of the library. Further, they may have a sequence comprising one or more recognition sites for restriction endonucleases added to one or both of their ends. The selected organism or group of organisms may be selected from prokaryotes and from eukaryotes; and in prokaryotes the consensus sequences to be retained most often will comprise the −35 signal (−35 to −30): TTGACA and the −10 signal (−12 to −7): TATAAT or parts of both comprising at least 3 conserved nucleotides of each, while in eukaryotes said consensus sequences should comprise a TATA box and at least one upstream activation sequence (UAS). Such artificial promoter libraries can be used, e.g., for optimizing the expression of specific genes in various selected organisms.
Owner:JENSEN PETER RUHDAL +1
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