119 results about "Nucleobase" patented technology

The disclosure provides, for example, double stranded DNA (dsDNA) molecules comprising one or more chemically modified nucleobases. In some embodiments, the dsDNA molecule is circular and comprises a first strand and a second strand, wherein the first strand comprises one or more chemically modified nucleobases, and the second strand is free of chemically modified nucleobases. In some embodiments, the dsDNA molecule comprises a promoter sequence and an effector sequence that encodes an effector.

The disclosure provides, for example, double stranded DNA (dsDNA) molecules comprising one or more chemically modified nucleobases. In some embodiments, the dsDNA molecule is circular and comprises a first strand and a second strand, wherein the first strand comprises one or more chemically modified nucleobases, and the second strand is free of chemically modified nucleobases. In some embodiments, the dsDNA molecule comprises a promoter sequence and an effector sequence that encodes an effector.

Described is a compound for substituting amino acids of proteins or peptides, wherein the compound has the formula (1)wherein the stereocenter C1* represents CH that either results in the D- or L-form of the compound of formula (1); A− is a negatively charged ion compensating the positive charge; X1 is H or an amine protecting group; X2 is OH, an ester residue or an amide residue or an activated carboxylic acid derivate to be used for the formation of an amide bond; Y1, Y2 and Y3 are independently from each other a C1-C6 alkyl, and Z1 and Z2 are independently from each other a nucleobase, a C1 to C16 alkyl group, an aromatic residue or a heteroaromatic residue, wherein the aromatic residue or the heteroaromatic residue contains one 5, 6, or 7-membered ring or two condensed 5, 6, or 7-membered rings sharing two carbon atoms, wherein the aromatic residue or the heteroaromatic residue can be substituted by a linear or branched C1 to C16 alkyl group and / or a further aromatic group. Furthermore, a method for preparing this compound and proteins and peptides containing this compound are disclosed.

Provided are systems for strand-specific editing of DNA, including mitochondrial DNA in humans. The systems provided herein comprise a nickase and a single-stranded (ss) DNA deaminase each, or together, associated with a double-stranded DNA binding polypeptide such that DNA editing occurs in an editing region. Also provided herein are components of the systems for editing DNA taught herein, and methods of use thereof.

This disclosure relates to the modified 3' region elements that confer improved therapeutic properties including, but not limited to, increased stability, increased expression, and / or a reduced innate immune response when introduced into a population of cells, even in the absence of a 5'-cap. The disclosure also provides polynucleotides (e.g., RNA molecules) containing modified 3' regions. In some embodiments of the disclosure, the modified 3' regions contain modified adenosines (e.g., 2'-0-methoxy- adenosine, 2'-fluoro-adenosine, or locked nucleic acid (LNA)-adenosine) and / or a modified thymidine (e.g., inverted deoxythymidine). In some embodiments of the disclosure, the modified 3' region may contain one or more modified internucleoside linkages (e.g., a phosphorothioate linkage) or modified nucleobase (e.g., N1-methyl-pseudouridine). The polynucleotides of the disclosure may be used to express a desired polypeptide in a subject, such as a subject having a disease or condition associated with a deficiency in the corresponding endogenous polypeptide.

The invention relates to antisense molecules and methods for modulating splicing of polyomavirus T antigen pre-mRNA. In one aspect the invention relates to an antisense oligonucleotide 12 to 30, preferably 17, 18, 19 or 20 to 30 nucleobases in length which comprises a sequence that is the reverse complement of a contiguous stretch of at least 12 nucleobases of a polyomavirus T-antigen pre-mRNA and which antisense oligonucleotide can modulate splicing of said T-antigen pre-mRNA in a cell.

Provided herein is a method of detecting the presence or absence of a single naturally- or synthetically-modified nucleobase in a polynucleotide molecule, which is achieved by first contacting the polynucleotide molecule with one or more reagents capable of attaching a detectable moiety to at least one nucleobase of the polynucleotide molecule or to a nucleobase adjacent to the modified nucleobase, thereby forming a labeled nucleobase, while the presence or absence of the modified nucleobase is determined by the attachment. The polynucleotide molecule is then assayed using a nanopore device to detection the presence or absence of the labeled nucleobase, wherein the detectable moiety attached to at least one nucleobase in the polynucleotide molecule has a molecular weight that ranges from 40 to 1,000 Daltons, and the average pore diameter in the nanopore device is no more than 5 nanometers.

This disclosure relates to reagents such as antisense oligonucleotides that bind to nucleic acids encoding cryptic exons, thereby inhibiting or preventing ELAVL3 cryptic splicing, and to their use in the treatment or prevention of TDP-43-related neurodegenerative or neurological diseases or conditions associated therewith. In some embodiments, the antisense oligonucleotide is a nucleobase polymer capable of reducing the level or expression of intracellular ELAVL3 cryptic exon RNA and increasing or restoring the expression of functional ELAVL3 protein without substantially incorporating the cryptic exon RNA peptide sequence.

Disclosed herein are improved methods and compositions of de novo synthesis of nucleic acids by cyclic extension using nucleotides that have an N-linked or O-linked scar or protecting group, and subsequent removal of the scar or protecting group. During polymerase-nucleotide conjugate-based polynucleotide synthesis or after the synthesis is completed, nucleobases having a scar from linker cleavage can be converted back into native form by removal of the scars from the nucleobases. Secondary structure formation in the nascent chain, which may inhibit extension reactions, is suppressed by the use of monomers with protected nucleobases that prevent Watson-Crick base pairing and / or other structures. After the synthesis is completed, the nucleobases can be converted back into native form by palladium-based removal of the protecting groups.

The invention features base editors having reduced non-target deamination, methods of using the base editors, and assays for characterizing base editors as having decreased non-target deamination, e.g. compared to programmed, on-target deamination.

The invention features nucleobase editors and multi-effector nucleobase editors having an improved editing profile with minimal off-target deamination, compositions comprising such editors, and methods of using the same to generate modifications in target nucleobase sequences.

Provided are a fusion protein useful for performing base editing, a method for performing gene editing in a cell at a target site, a dual guide RNA system, and a guide RNA.SOLUTION: To provide fusion proteins and related molecules useful for performing base editing with reduced or no off-target mutations. The fusion protein can comprise a first fragment comprising a nucleobase deaminase or a catalytic domain thereof, a second fragment comprising a nucleobase deaminase inhibitor, and a protease cleavage site between the first fragment and the second fragment. Also provided are improved prime editing systems comprising prime editing guide RNAs with improved stability.SELECTED DRAWING: None

The present invention provides a method of replacing a pathogenic amino acid using a programmable base editor system comprising a polynucleotide programmable nucleotide binding domain and a nucleobase editing domain conjugated to a guide polynucleotide. The invention also provides a base editor system for editing nucleobases of a target nucleotide sequence.

Disclosed herein is a modified oligonucleotide, the modified oligonucleotide comprises one or more modifications in at least one of a phosphate backbone, a nucleobase, or a sugar. The one or more modifications impede translocation through a nanopore by increasing non-covalent interactions with the interior of the nanopore or the lipid bilayer that supports the nanopore, increasing the bulk size or the steric hinderance of oligonucleotide, or alter the charge density of the oligonucleotide.

The present disclosure relates to compounds of Formula (I) which are incorporated into DNA for on-DNA aldehyde capture and use as fluorescent molecular rotors.

Provided are: a method for producing a compound useful as a nucleotide prodrug; a compound useful as a starting material or an intermediate of the production method; and a nucleotide prodrug precursor.　A method for producing a compound according to the present invention comprises: an aryloxylation step for reacting a compound (1) with a phenol compound ArOH to obtain a compound (2); an oxidative halogenation step for oxidatively halogenating the compound (2) with a halogenating agent to obtain a compound (3); and an amination step for reacting the compound (3) with a compound (5) to obtain a compound (4). In the formula, R11-R15 are a hydrogen atom, etc., R1 is an optionally substituted aryl group, R2-R4 are a hydrogen atom, etc., R5 is an optionally substituted alkyl group, R6 is an amino acid side chain, etc., Ar is an optionally substituted aryl group, X is a halogenyl group, A- is a counter anion, and Bs represents a nucleic acid base optionally having a protecting group.

Nucleic acid products and compositions and their uses are provided. In particular, nucleic acid products are provided that modulate, interfere with, or inhibit APOC3 gene expression. The products can be oligomeric compounds that comprise at least a first region of linked nucleosides having at least a first nucleobase sequence that is at least partially complementary to at least a portion of RNA transcribed from a APOC3 gene, wherein said first nucleobase sequence is selected from the following sequences, or a portion thereof: SEQ ID NOs 1 to 39

The present invention relates to a light-activatable photocaged conjugate, which, upon activation, is capable of inducing an immune response, wherein said conjugate comprises: (a) at least one double-stranded oligonucleotide, comprising: (i) a first strand of a ribonucleic acid having a length of at least eight nucleotides; and (ii) a second strand of a ribonucleic acid having a length of at least eight nucleotides and forming complementary base pairs with the first strand; and (b) at least one photoremovable protecting group (PPG); wherein the at least one PPG is coupled to a ribose at the 2'-O-position or a nucleobase of a nucleotide in the first or second strand of the at least one double-stranded oligonucleotide according to item (a). The present invention moreover provides a pharmaceutical composition, a drug delivery system, an adjuvant, a vaccine and kit for use in medicine, each of them comprising a conjugate according to the invention. The present invention also relates to said conjugate for use as a medicament, for use as a vaccine, for use as an adjuvant, for use in a method of treatment or prevention of a disease, for use in a method of infiltrating immune cells, preferably T cells, and for use in a method of turning cold into hot tumours.

Among other things, the present disclosure provides oligonucleotide compositions and methods thereof. In some embodiments, oligonucleotides comprise various chemical modifications of sugars, nucleobases, and / or mtemucleotidic linkages and patterns thereof and are useful for exon skipping. In some embodiments, the present disclosure provides technologies useful for skipping exon 45 of dystrophin (DMD) transcripts. In some embodiments, the present disclosure provides technologies useful for modulating DMD transcript splicing. In some embodiments, the present disclosure provides methods for preventing or treating conditions, disorders or diseases including Duchenne muscular dystrophy.

Methods for detecting modified nucleobases in a DNA sample by excising a modified nucleobase of interest using a specific DNA glycosylase are described. Prior to the glycosylase treatment, the DNA target fragment is copied by a DNA polymerase to produce a complementary copy strand that retains genetic information of the DNA target strand. After glycosylase treatment, the DNA target fragment is repaired by: linking across a nick to produce a deletion at each position of the modified nucleobase of interest; or filling the nicks with a single non-natural nucleotide to produce a base substitution at each position of the modified nucleobase of interest. The comparison of the DNA sequences of the two strands of the target fragment enables the recognition of the positions of the modified nucleotide bases in the DNA target fragment.

Described are methods of detecting modified nucleotide bases in a DNA sample using specific DNA glycosylases to excise a modified nucleobase of interest. Prior to glycosylase treatment, DNA target fragments are copied by a DNA polymerase to produce a complementary copy strand that preserves the genetic information of the DNA target strand. Following glycosylase treatment, the DNA target fragments are repaired by either ligating across the gaps to produce a deletion at each position of the modified nucleobase of interest or filling in the gaps with a single non-native nucleotide to produce a base substitution at each position of the modified nucleobase of interest. Comparison of the DNA sequences of the two strands of the target fragments enables identification of the positions of the modified nucleotide base in the DNA target fragment.

Methods, systems, and non-transitory computer-readable media are disclosed for accurately and efficiently detecting when a bubble is affecting a nucleic acid sequencing run based on data captured (or derived from) during base callings during the sequencing run. Specifically, in one or more embodiments, the disclosed systems receive data identifying nucleobase callings and data identifying quality indicators for the nucleobase callings during a sequencing cycle. Based on a particular nucleobase calling and a threshold marking for the quality indicator, the disclosed systems utilize a machine learning model to detect the presence of a bubble in a nucleotide sample slide. In addition to simply detecting the presence of a bubble, the disclosed systems can also classify different detected bubbles, such as air bubbles, oil bubbles, or ghost bubbles, or other outputs during sequencing. By utilizing the call data and quality indicators, the disclosed systems can use readily available sequencing data in a platform-agnostic approach to detect bubbles using a uniquely trained machine learning model.

The invention relates to a conjugate comprising or consisting of (a) at least one molecule capable of specifically binding to at least one analyte; and at least one nucleic acid nanostructure (b); wherein said nucleic acid nanostructure of (b) comprises a plurality of single-stranded oligonucleotides; and wherein at least two of said plurality of oligonucleotides each comprise a first identical nucleobase sequence.

Nucleotides with alpha-imino phosphate groups and bridging sulfurs, and methods of synthesizing and using the same, are provided herein. In some examples, a nucleotide may include a sugar, a nucleobase coupled to the sugar, an alpha-imino phosphate group, and a bridging sulfur coupling the alpha-imino phosphate group to the sugar.

To provide antisense compounds, compositions, and methods for decreasing PKK mRNA and protein expression, which are useful for treating, preventing, or ameliorating PKK-associated diseases, disorders, and conditions.SOLUTION: Provided is a compound comprising a modified oligonucleotide and a conjugate group, where the modified oligonucleotide consists of 12-30 linked nucleosides and has a nucleobase sequence comprising at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, or at least 20 consecutive nucleobases of any of the nucleobase sequences of the specific sequences Nos. 30 to 2226.SELECTED DRAWING: None

This disclosure describes embodiments of methods, systems, and non-transitory computer readable media that can quickly and accurately determine equalizer coefficients for an equalizer based on estimated point-spread-function values and estimated noise values derived from expected response signals of oligonucleotide clusters. For example, the disclosed systems can receive signal values for expected response signals from one or more clusters of oligonucleotides incorporating labeled nucleobases. Based on the signal values, the disclosed systems can determine estimated point-spread-function values for one or more such clusters of oligonucleotides and estimated noise values within a channel. From the estimated point-spread-function values and the estimated noise values, the disclosed systems can determine equalizer coefficients that compensate for the estimated point-spread-function values and the estimated noise values. The disclosed systems can further determine a base call for one or more such clusters of oligonucleotides by utilizing the equalizer coefficients.

The disclosure provides, for example, double stranded DNA (dsDNA) molecules comprising one or more chemically modified nucleobases. In some embodiments, the dsDNA molecule is circular and comprises a first strand and a second strand, wherein the first strand comprises one or more chemically modified nucleobases, and the second strand is free of chemically modified nucleobases. In some embodiments, the dsDNA molecule comprises a promoter sequence and an effector sequence that encodes an effector.

This disclosure describes methods, non-transitory computer readable media, and systems that account for spontaneous deamination, sequencing errors, and / or methylation of nucleobases to more accurately predict genotype from reads of a sample. The disclosed systems can estimate a first set of probabilities that a sample exhibits observed duplex consensus bases at a genomic coordinate given converted haplotype intermediate bases. The disclosed system can also determine a second set of probabilities that the sample exhibits converted haplotype intermediate bases given an underlying haplotype. Using a variant caller, the disclosed systems can determine a third set of probabilities of the sample exhibiting the observed duplex consensus bases at the genomic coordinate given candidate haplotype bases based on the first and second sets of probabilities. The disclosed systems may further use the third set of probabilities to determine posterior genotype probabilities and generate a genotype call.

The invention discloses thymine-containing polyolefin as well as a preparation method and application thereof, the structural formula of the polyolefin is shown in the specification, x is equal to 100-400, and R is phenyl. Norbornene monomer NBT containing nuclear basic groups is synthesized and is copolymerized with cyclooctene (COE) through ring-opening metathesis polymerization (ROMP), and long-chain alkane is introduced to improve the toughness of the polymer; and a series of polymers with ultra-high molecular weight are synthesized by changing the proportion. The NBT in the polymer enables the polymer to have good hydrophobic performance, and the NBT as a hot melt adhesive has good adhesion performance to different substrates.

To provide a method for treating a human subject having a disease or disorder suitable for antisense oligonucleotide therapy comprising an effective amount of an antisense oligonucleotide or an antisense oligonucleotide conjugate, or a pharmaceutically acceptable salt thereof.SOLUTION: In some embodiments, nucleobases of the antisense oligonucleotide are linked to a morpholino ring structure. In some embodiments, morpholino subunits are connected by a phosphorus-containing intersubunit linkage that joins the morpholino nitrogen of one subunit to the 5'-exocyclic carbon of an adjacent morpholino subunit.SELECTED DRAWING: None