28 results about "Nucleobase" patented technology

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.

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.

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.

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

The present invention features genetically modified immune cells comprising novel adenosine base editors (e.g., ABE8) having enhanced anti-neoplasia activity, resistance to immune suppression, and decreased risk of eliciting a graft-versus-host reaction or host-versus-graft reaction, or a combination thereof. The present invention also features methods for producing and using these modified immune effector cells.

This disclosure provides, in particular, oligonucleotide compositions and methods thereof. In some embodiments, the oligonucleotides comprise various chemical modifications of sugars, nucleobases, and / or internucleotide bonds and their patterns, and are available for exon skipping. In some embodiments, this disclosure provides techniques for use with exon 51 of a jumping dystrophin (DMD) transcript. In some embodiments, this disclosure provides techniques for modulating DMD transcript splicing. In some embodiments, this disclosure provides methods for preventing or treating conditions, disorders, or diseases including Duchenne muscular dystrophy.

The present disclosure provides compositions and methods related to analyzing DNA, such as cell-free DNA. In some embodiments, the cell-free DNA is from a subject having or suspected of having cancer and / or the cell-free DNA includes DNA from cancer cells. In some embodiments, the DNA is contacted with a methylation-discriminating nuclease, thereby degrading methylated or unmethylated DNA to produce a treated sample, and the treated sample is subjected to a procedure that affects a first nucleobase differently from a second nucleobase to produce a treated and converted sample. In some embodiments, the DNA is subjected to a procedure that affects a first nucleobase differently from a second nucleobase to produce a converted sample and the converted sample is contacted with a methylation-discriminating nuclease, thereby degrading methylated or unmethylated DNA to produce a treated and converted sample.

本文提供了用于可以应用于双链体扩展测序的文库制备的方法。特别地，本发明涉及用于生成双链体核酸构建体的方法，所述双链体核酸构建体用作 Xpandomer 合成及其纳米孔序列确定的模板，从而在单次运行中提供来自 DNA 靶片段的两条链的序列信息。本发明还提供了用于使用双链体模板构建体进行表观遗传分析的方法，所述双链体模板构建体包括源自文库片段的可以包括经修饰的核碱基的亲代链和包括天然核碱基的新合成的互补子代拷贝链。本发明还涉及用于合成双链体核酸模板的 Xpandomer 拷贝的改进的反应条件。还提供了用于所述方法的组合物和试剂盒。

Disclosed are conjugates of an oligonucleotide and a peptide covalently bonded or linked via a linker to the oligonucleotide, the peptide including at least one cationic domain comprising at least 4 amino acid residues and at least one hydrophobic domain comprising at least 3 amino acid residues, provided that the peptide includes a total of 7 to 40 amino acid residues and does not include any artificial amino acid residues; and the oligonucleotide including a total of 12 to 40 contiguous nucleobases, where at least 12 contiguous nucleobases are complementary to a target sequence in a human dystrophin gene.

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 internucleotidic linkages and patterns thereof and are usefill for exon skipping. In some embodiments, the present disclosure provides technologies useful for skipping cryptic exons of stathmin-2(STMN2) transcripts. In some embodiments, the present disclosure provides technologies useful for modulating STMN2 transcript splicing. In some embodiments, the present disclosure provides methods for preventing or treating conditions, disorders or diseases including neurodegenerative diseases, e.g,, amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).

The present disclosure provides methods for reducing sequencing errors comprising one or any combination of: (i) removing deaminated bases in any nucleic acid molecule throughout a library preparation workflow which includes immobilised splints which bind to the library, the use of a compaction oligonucleotide, optionally with an intervening sequence, formation of closed circular nucleic acids, creating gaps using glycosylase and lyase activities at positions with deaminated bases. The library may be sequenced using pairwise sequencing, e.g. with dark sequencing and / or sequencing using a multivalent labelled probe for the formation of an avidity molecule and soluble primer and polymerase. Method for sequencing concatemers in which the concatermers are contacted with polymerases, soluble primers and a multivalent labelled molecule which forms a complex with the polymerase. Detecting polymerase position and nucleobase bound to the polymerase in the complex. These methods generate higher quality base calls during downstream sequencing workflows.

The disclosure features compositions and methods for treating cardiovascular disease by introducing one or more alterations into a lipoprotein(a) (LPA) polynucleotide in a cell. In particular embodiments, the disclosure provides a base editor system (e.g., a fusion protein or complex comprising a programable DNA binding protein, a nucleobase editor, and gRNA) for modifying an LPA polynucleotide, where the modification is associated with reduced expression, and / or reduced activity of the LPA polypeptide encoded by the polynucleotide.

This disclosure provides, in particular, oligonucleotide compositions and methods thereof. In some embodiments, the oligonucleotides comprise various chemical modifications of sugars, nucleobases, and / or internucleotide bonds and their patterns, and are available for exon skipping. In some embodiments, this disclosure provides techniques for use with exon 44 of a jumping dystrophin (DMD) transcript. In some embodiments, this disclosure provides techniques for modulating DMD transcript splicing. In some embodiments, this disclosure provides methods for preventing or treating conditions, disorders, or diseases including Duchenne muscular dystrophy.

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 internucleotidic 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.

This disclosure provides, in particular, oligonucleotide compositions and methods thereof. In some embodiments, the oligonucleotides comprise various chemical modifications of sugars, nucleobases, and / or internucleotide bonds and their patterns, and are usable for exon skipping. In some embodiments, this disclosure provides techniques for use in exon 52 of jumping dystrophin (DMD) transcripts. In some embodiments, this disclosure provides techniques for modulating DMD transcript splicing. In some embodiments, this disclosure provides methods for preventing or treating conditions, disorders, or diseases including Duchenne muscular dystrophy.

The present invention provides methylcytosine selective deaminases, compositions, kits, and methods of using the thereof, including sequencing methods involving: (a) contacting a DNA substrate comprising cytosine (C) and at least one methylcytosine nucleobase selected from 5-methylcytosine (5mC) and 5-hydroxymethylcytosine, or comprising C and both 5mC and 5hmC, with a methylcytosine selective deaminase to produce a deamination product, wherein the methylcytosine selective deaminase (i) is capable of deaminating 5mC to thymidine (T) and / or deaminating 5hmC to hydroxymethyluridine (hmU), and (ii) preferentially deaminating at least one methylcytosine nucleobase relative to cytosine (C); and (b) sequencing the deamination product, or amplifying the deamination product to produce an amplification product, and sequencing the amplification product to produce a sequence read in each case, wherein the position of C and the position of at least one methylcytosine nucleobase in the DNA substrate are determined based on the sequence read.

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 internucleotidic linkages and patterns thereof and are useful for exon skipping. In some embodiments, the present disclosure provides technologies useful for skipping exon 51 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.

The invention discloses engineered RNA-guided DNA-binding (RGDB) variants, especially of the Lachnospiraceae bacterium CRISPR-Casl2a (LbCasl2a) that exhibit superior performance, like enhanced specific binding to target DNA sequences, reduced non-specific DNA binding, or reduced catalytic activity. By introducing numerous substitution mutations across distinct structural blocks, the variants achieve stronger, more specific binding to target DNA while markedly reducing off-target or non-specific interactions. A second tier of mutations targets catalytic residues and other functional sites to generate catalytically inactive forms (dRGDP) that retain DNA-binding capability. These RGDB scaffolds can be fused to diverse effector domains, including transcriptional regulators, epigenetic modifiers, or nucleases, to modulate gene expression or repair defective genes in mammalian or plant cells. When coupled with base-editing enzymes such as adenosine or cytosine deaminases, the resulting adenine or cytosine base editors display enhanced editing efficiency and altered editing windows, enabling precise conversion of additional nucleobases.

The invention provides a compound of formula: (I), (II) and (III) or a salt thereof, wherein R1-R4, R4a, Rh and Ri have any of the values described in the specification, as well as compositions comprising a compound of formula (I), (II), and (III). The compounds are useful to treat viral infections, for example, when administered in combination with an antiviral nucleobase.

The present invention features genetically modified immune cells comprising novel adenosine base editors (e.g., ABE8) having enhanced anti-neoplasia activity, resistance to immune suppression, and decreased risk of eliciting a graft-versus-host reaction or host-versus-graft reaction, or a combination thereof. The present invention also features methods for producing and using these modified immune effector cells.

This document discloses prodrugs of nucleosides, nucleotides, or nucleobases or their analogues, wherein the prodrug is a compound of formula I: or a pharmaceutically acceptable salt thereof, nanoparticles comprising the compound, pharmaceutical compositions comprising the compound or nanoparticles, and methods of using the prodrugs.

This specification provides MAPT antisense oligonucleotides that can modulate the expression of MAPT target nucleic acids. Methods of using them are also provided. In certain embodiments, a MAPT antisense oligonucleotide (MAPT ASO) is provided comprising a nucleic acid sequence comprising at least nine consecutive nucleobases of sequences selected from any of SEQ ID NOs: 4-9 and 19-37, and at least one modified internucleoside bond and / or at least one modified sugar.

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

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.

Among other things, the present disclosure provides RHO oligonucleotides, compositions, and methods. In some embodiments, provided oligonucleotides comprise nucleobase modifications, sugar modifications, internucleotidic linkage modifications and / or patterns thereof, and have improved properties, activities and / or selectivities. In some embodiments, the present disclosure provides RHO oligonucleotides, compositions and methods for preventing and / or treating RHO-related conditions, disorders or diseases, such as retinopathy (e.g, retinal degeneration, retinal degenerative disease, retinal degenerative disorder, inherited retinal degenerative disorder, retinitis pigmentosa, autosomal dominant retinitis pigmentosa, etc.).

This disclosure provides inhibin subunit βE (INHBE)-related double-stranded oligonucleotides, compositions, and methods of using such double-stranded oligonucleotides and compositions for the prevention and / or treatment of various conditions, disorders, or diseases associated with INHBE expression. In some embodiments, the provided double-stranded oligonucleotides and compositions comprise nucleobase modifications, sugar modifications, internucleotide linking modifications, and / or patterns thereof, and have improved properties, activity, and / or selectivity. In some embodiments, the provided double-stranded oligonucleotides and compositions target INHBE.

This disclosure provides, in particular, oligonucleotide compositions and methods thereof. In some embodiments, the oligonucleotides comprise various chemical modifications of sugars, nucleobases, and / or internucleotide bonds and their patterns, and are available for exon skipping. In some embodiments, this disclosure provides techniques for use with exon 45 of jumping dystrophin (DMD) transcripts. In some embodiments, this disclosure provides techniques for modulating DMD transcript splicing. In some embodiments, this disclosure provides methods for preventing or treating conditions, disorders, or diseases including Duchenne muscular dystrophy.