53 results about "Single stranded oligonucleotides" patented technology

The present application relates to siRNA and oligonucleotide agents for use in the prevention or treatment of SOD1-related neurodegenerative diseases or conditions, such as amyotrophic lateral sclerosis, ALS. The oligonucleotide agent comprises a double-stranded targeting oligonucleotide (siRNA) and a non-targeting single-stranded oligonucleotide (ACO), wherein the siRNA targets the mRNA region of the target gene SOD1.

The application discloses an oligonucleotide hydrogel and a preparation method and application thereof, and comprises the following steps: sequentially adding oligonucleotide and PBS buffer into a metal salt solution to obtain a mixed solution; placing the mixed solution in a shaking table and oscillating and incubating; after incubation, centrifuging, discarding the supernatant and reserving the precipitate; resuspending the precipitate by adding deionized water, centrifuging, discarding the supernatant and washing to obtain the hydrogel; the application only needs single-stranded oligonucleotide, has no special requirements on the sequence composition and structure of the oligonucleotide, does not need special design, can be assembled with divalent and trivalent metal ions, has a simple process, is easy to operate, and can wrap biological enzymes in the hydrogel, realizes enzyme immobilization and recycling.

A system for analyzing biological components in a biological sample, wherein the system comprises a planar surface, and wherein the system is configured to perform a procedure comprising: (a) arranging a spatially connected biological sample adjacent to the planar surface, wherein: the spatially connected biological sample comprises a tissue sample, the tissue sample comprises a plurality of cells, the planar surface comprises glass, plastic, or a combination thereof, the planar surface further comprises a plurality of binding sites, the plurality of binding sites is arranged in a two-dimensional pattern on the planar surface, the planar surface comprises at least 10⁵ binding sites, each of the plurality of binding sites comprises a plurality of single-stranded oligonucleotides, and the plurality of single-stranded oligonucleotides is coupled to the planar surface.at least one subset of the plurality of single-stranded oligonucleotides comprises: (i) a binding sequence comprising a plurality of thymine bases configured to bind to poly-A sequences, (ii) a unique molecular identifier, (iii) a barcode associated with a position on the planar surface, and (iv) a sequencing primer, and each oligonucleotide of the subset of the plurality of single-stranded oligonucleotides comprises at least 50 nucleotides; (b) imaging at least a portion of the spatially linked biological sample, wherein the imaging comprises bright-field imaging, phase-contrast imaging, fluorescence imaging, or a combination thereof; (c) releasing nucleic acids from the spatially linked biological sample; and (d) capturing at least one subset of the nucleic acids on at least the subset of single-stranded oligonucleotides, thereby recovering the captured nucleic acids.the captured nucleic acids are immobilized on the flat surface.

This invention provides a preventive and / or therapeutic agent for cystic kidney disease. The preventive and / or therapeutic agent for cystic kidney disease comprises a single-stranded oligonucleotide containing a base sequence complementary to at least a portion of the base sequence of miR-21.

To provide an aptamer that binds to an S protein of SARS-CoV-2 omicron variant.SOLUTION: Provided is a nucleic acid aptamer having binding ability to SARS-CoV-2, where the nucleic acid aptamer includes a single strand oligonucleotide having a nucleotide as a constitutional unit, the single strand oligonucleotide includes a loop region, a 3' stem region bonded to a 3' terminal of the loop region, and a 5' stem region bonded to a 5' terminal of the loop region, the base number of the loop region is 16 to 50 mer, the base number of the 3' stem region is 5 mer or more, the base number of the 5' stem region is 5 mer or more, and the 3' stem region and the 5' stem region have mutually complementary base sequences.SELECTED DRAWING: Figure 1

A single-stranded oligonucleotide having a length of 16-30 nucleotides. The single-stranded oligonucleotide and complement component C3 (CC3) mRNA have sufficient complementarity to mediate RNAi effect; each nucleotide in the single-stranded oligonucleotide is a modified or unmodified nucleotide, at least one nucleotide in the single-stranded oligonucleotide is a nucleotide X, and the at least one nucleotide is a fluoro-modified nucleotide; moreover, according to a direction from the 5' end to the 3' end, at least one nucleotide X is located after an eighth nucleotide and is spaced apart from the eighth nucleotide in the single-stranded oligonucleotide by 4-7 nucleotides; and each nucleotide X is a deoxynucleotide or an unmodified nucleotide. The present invention further relates to a double-stranded oligonucleotide comprising the single-stranded oligonucleotide as an antisense strand, an oligonucleotide conjugate, and a pharmaceutical composition.

A single-stranded oligonucleotide having a length of 16-30 nucleotides. The composition of the single-stranded oligonucleotide enables the single-stranded oligonucleotide to inhibit the expression of target mRNA by means of an RNAi mechanism. Each nucleotide in the single-stranded oligonucleotide is independently a modified or unmodified nucleotide, wherein at least one nucleotide in the single-stranded oligonucleotide is a nucleotide X; at least one nucleotide is a fluoro-modified nucleotide; and, in the 5' to 3' direction, the 13th nucleotide of the single-stranded oligonucleotide is a substituted alkoxy-modified nucleotide, the 14th nucleotide of the single-stranded oligonucleotide is a nucleotide X, and each of the 15th nucleotide and all subsequent nucleotides of the single-stranded oligonucleotide is independently a modified nucleotide. A double-stranded oligonucleotide comprising the single-stranded oligonucleotide as an antisense strand, an oligonucleotide conjugate and a pharmaceutical composition.

The present disclosure relates to methods of inhibiting in a subject in need thereof, the RNAi inhibitory activity of a double stranded ribonucleic acid (dsRNA) agent, or a salt thereof, that inhibits the expression of an angiotensinogen (AGT) gene; ameliorating in a subject in need thereof, a side effect of a dsRNA agent, or a salt thereof, that inhibits the expression of an AGT gene; and / or treating a subject in need thereof, previously administered a dsRNA agent, or a salt thereof, that inhibits the expression of an angiotensinogen AGT gene, by administering to the subject a fixed dose of a single stranded oligonucleotide, and compositions thereof.

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.

The present invention relates to 5'-modified nucleoside analogs and oligonucleotides produced therefrom, and more specifically, to modified nucleosides and their analogs that can be used to be incorporated into the oligonucleotide terminus, which can be bound to double-stranded oligonucleotides (short interfering RNA) or single-stranded oligonucleotides (e.g., antisense oligonucleotides). The oligonucleotides provided herein are expected to result in the loss of normal function of the target RNA by hybridizing to a portion of the target RNA.

This invention provides a method for screening highly specific nucleic acid aptamers and specific *Lactobacillus helveticus* aptamers, belonging to the field of nucleic acid aptamers. Specifically, the method for screening highly specific nucleic acid aptamers provided by this invention includes the following steps: S1: A second library is obtained after N rounds of forward screening of a first library; S2: A third library is obtained after M rounds of reverse screening of the second library; S3: The third library is obtained after X rounds of forward screening of the third library to obtain selected random single-stranded oligonucleotides, which are then subjected to PCR amplification, purification, cloning, and sequencing; S4: The sequences cloned and sequenced in step S3 are used for affinity and specificity assays to select sequences with high affinity and specificity, thereby obtaining highly specific nucleic acid aptamers. The aptamers provided by this invention have the advantages of high specificity and strong affinity, and the construction method of the aptamers provided by this invention has the advantage of short screening time.

The invention relates to the technical field of molecular biology, in particular to a structural probe and application thereof. The invention provides a nucleic acid probe which is single-stranded oligonucleotide, and the single-stranded oligonucleotide has a stem-loop structure; the number of the stem rings is larger than or equal to 2. The detection method provided by the invention is high in sensitivity, has ultrahigh sensitivity higher than that of a common single-chain fluorescent probe as an RNase reaction substrate, and can detect RNase A as low as 0.1 pg / ml. The probe disclosed by the invention has broad spectrum and has detection capability on various ribonuclease.

Aspects of the present application provide methods for analyzing tissue samples. The methods may include disposing a tissue sample on a surface. The tissue sample may be imaged. In certain aspects, nucleic acids from the tissue sample may also be analyzed. In some such aspects, the surface can include a plurality of capture sites that contain single-stranded oligonucleotides, and nucleic acids from the tissue sample may be captured using at least a subset of the single-stranded oligonucleotides.

The present disclosure provides a single-stranded oligonucleotide, wherein the single-stranded oligonucleotide has a length of 16-30 nucleotides and can inhibit the expression of APOE4 mRNA by the mechanism of RNA interference (RNAi); wherein each nucleotide in the single- stranded oligonucleotide independently of one another is a modified or unmodified nucleotide; and wherein at least one nucleotide is a nucleotide X, and at least one nucleotide is a fluoro modified nucleotide; and in a 5' to 3' direction, in the single-stranded oligonucleotide, the 13th nucleotide is a substituted alkoxy modified nucleotide; the 14th nucleotide is a nucleotide X; and each of the 15th nucleotide and all the subsequent nucleotides independently of one another is a modified nucleotide; and each nucleotide X is independently a deoxyribonucleotide or an unmodified nucleotide. The present disclosure also provides a double-stranded oligonucleotide, an oligonucleotide conjugate and a pharmaceutical composition comprising the single-stranded oligonucleotide as an antisense strand.

One aspect of the present invention relates to a single-stranded oligonucleotide having a having a sequence represented by formula (I): (5′-Z1-3′)-Q1-L-Q2-(5′-Z2-3′) (I). In formula (I), Z1 is a first oligonucleotide, comprising 15-100 optionally modified nucleotides that is substantially complementary to a target gene; Z2 is a second oligonucleotide, comprising 15-100 optionally modified nucleotides that is substantially complementary to Z1; and Z1 and Z2 are capable of forming an intra-strand duplexed region comprising 3 or more consecutive base pairs. L is a linking group. Q1 and Q2 each independently represent 0 to 12 optionally modified nucleotides. At least one nucleotide in formula (I) is a modified nucleotide. Other aspects of the invention relate to a pharmaceutical composition and a method for inhibiting the expression of one or more target gene in a subject.

Provided is a single-stranded oligonucleotide having a length of 16-30 nucleotides. The single-stranded oligonucleotide and APOC3mRNA have sufficient complementarity to mediate an RNAi effect. Each nucleotide in the single-stranded oligonucleotide is a modified or unmodified nucleotide. At least one nucleotide in the single-stranded oligonucleotide is a nucleotide X, and at least one nucleotide is a fluoro-modified nucleotide. In the direction from the 5' end to the 3' end, at least one nucleotide X is located after the eighth nucleotide of the single-stranded oligonucleotide and spaced apart from the eighth nucleotide of the single-stranded oligonucleotide by 4-7 nucleotides. Each nucleotide X is a deoxynucleotide or an unmodified nucleotide. Further provided are a double-stranded oligonucleotide comprising the single-stranded oligonucleotide as an antisense strand, an oligonucleotide conjugate, and a pharmaceutical composition.

The present disclosure relates to multimeric oligonucleotides comprising subunits, each of the subunits independently comprises a single-stranded or double-stranded oligonucleotide. Each of the subunits is joined to another subunit by a covalent linker, and at least one subunit comprises at least one partial single-stranded oligonucleotide. The present disclosure also relates to methods of synthesizing the multimeric oligonucleotides and the methods of using the multimeric oligonucleotides disclosed herein.

One aspect of the invention relates to a single-stranded oligonucleotide having a sequence represented by Formula (II) or (III): (5 '-Z11-3')-L-QS-(5 '-Z12-3') (II), (3 '-Z11-5')-L-QS-(3 '-Z12-5') (III), in Formula (II) or (III), Z11 is a first oligonucleotide comprising 15 to 100 optionally modified nucleotides that are substantially complementary to a target gene; z12 is a second oligonucleotide comprising from 10 to 100 optionally modified nucleotides that are substantially complementary to Z11; z11 and Z12 are capable of forming an intra-chain double-chain region comprising seven or more contiguous base pairs; qS represents from 0 to 12 optionally modified nucleotides; l is an optional linking group; at least one nucleotide in formula (II) is a modified nucleotide; and at least one nucleotide in formula (III) is a modified nucleotide wherein, for formula (II), at least one nucleotide at the 3 '-terminus of Z11, or for formula (III), at least one nucleotide at the 5'-terminus of Z11, together with L and QS, forms a loop region linking Z11 and Z12.

The application discloses a terminal transferase mutant, a recombinant protein, a nucleic acid molecule and a method for single-base extension of oligonucleotide, and relates to the technical field of oligonucleotide synthesis. The terminal transferase mutant has at least 80% identity with the amino acid sequence shown in SEQ ID NO:1, and has amino acid mutations in at least one of the following positions: R323, W427 and R438. Compared with a wild-type terminal transferase, the catalytic domain amino acid of the terminal transferase mutant is changed, and the catalytic capacity for a 3'-O-closed group triphosphate nucleoside is significantly improved, so that the 3'-O-closed group triphosphate nucleoside is efficiently coupled to a single-stranded oligonucleotide chain. On this basis, the application also develops a method for single-base extension of oligonucleotide. The method has technical advantages such as no need to control humidity, less use of chemical reagents, higher product purity, less chemical synthesis byproducts and the like.

Provided is a single-stranded oligonucleotide capable of inhibiting the expression of PNPLA3 mRNA by means of an RNAi mechanism. The length of the single-stranded oligonucleotide is 16-30 nucleotides. Each nucleotide in the single-stranded oligonucleotide is independently a modified or unmodified nucleotide. At least one nucleotide is a nucleotide X, and at least one nucleotide is a fluoro-modified nucleotide. Moreover, in the 5' to 3' direction, the 13th nucleotide is a substituted alkoxy-modified nucleotide; the 14th nucleotide is a nucleotide X; and each of the 15th nucleotide and all subsequent nucleotides is independently a modified nucleotide. Also provided are a double-stranded oligonucleotide comprising the single-stranded oligonucleotide as an antisense strand, an oligonucleotide conjugate, and a pharmaceutical composition.

Provided is a single-stranded oligonucleotide which can inhibit AGT mRNA expression via the RNAi mechanism and has a length of 16-30 nucleotides, wherein each nucleotide is independently a modified or unmodified nucleotide, at least one nucleotide is a nucleotide X, and at least one nucleotide is a fluoro-modified nucleotide; furthermore, along the 5'-end-to-3'-end direction, the 13th nucleotide is a nucleotide modified with a substituted alkoxy group, the 14th nucleotide is a nucleotide X, and each of the 15th nucleotide and all the nucleotides thereafter is independently a modified nucleotide. Further provided are a double-stranded oligonucleotide containing the single-stranded oligonucleotide as an antisense strand, an oligonucleotide conjugate, and a pharmaceutical composition.

Provided is a single-stranded oligonucleotide having a length of 16-30 nucleotides. The single-stranded oligonucleotide has complementarity to FXI mRNA sufficient to mediate the RNAi effect. Each nucleotide in the single-stranded oligonucleotide is either modified or unmodified, wherein in the single-stranded oligonucleotide, at least one nucleotide is nucleotide X and at least one nucleotide is a fluoro-modified nucleotide. Furthermore, in the direction from the 5' end to the 3' end, at least one nucleotide X is located after the 8th nucleotide of the single-stranded oligonucleotide and is spaced apart from the 8th nucleotide of the single-stranded oligonucleotide by 4 to 7 nucleotides; and each nucleotide X is either a deoxynucleotide or an unmodified nucleotide. Further provided are a double-stranded oligonucleotide, an oligonucleotide conjugate and a pharmaceutical composition that comprise the single-stranded oligonucleotide as an antisense strand.

Provided is a single-stranded oligonucleotide having a length of 16-30 nucleotides. The single-stranded oligonucleotide has sufficient complementarity with a target mRNA to mediate RNAi; and each nucleotide in the single-stranded oligonucleotide is a modified or unmodified nucleotide, wherein at least one nucleotide in the single-stranded oligonucleotide is a nucleotide X, and at least one nucleotide is a fluoro-modified nucleotide. Moreover, according to the direction from the 5' end to the 3' end, at least one nucleotide X is located after the eighth nucleotide of the single-stranded oligonucleotide and is spaced apart from the eighth nucleotide of the single-stranded oligonucleotide by 4-7 nucleotides. Provided are a double-stranded oligonucleotide comprising the single-stranded oligonucleotide as an antisense strand, an oligonucleotide conjugate, and a pharmaceutical composition.

Described are 5′-cyclo-phosphonate modified nucleotides, and oligonucleotides, such as interference (RNAi) agents, containing 5′-cyclo-phosphonate modified nucleotides. The RNAi agents having either double-stranded or single-stranded oligonucleotides described herein comprising 5′cyclo-phosphonate modified nucleotides are useful in modulating gene expression as well as therapeutic, diagnostic, target validation, and genomic discovery applications. The RNAi agents and single-stranded antisense oligonucleotides comprising 5′-cyclo-phosphonate modified nucleotides are useful in the treatment of diseases or conditions that respond to inhibition of gene expression or activity in a cell, tissue, or organism.

The present disclosure provides a single-stranded oligonucleotide, wherein the single-stranded oligonucleotide has a length of 16-30 nucleotides and can inhibit the expression of PCSK9 mRNA by the mechanism of RNA interference (RNAi); wherein each nucleotide in the single- stranded oligonucleotide independently of one another is a modified or unmodified nucleotide; and wherein in the single-stranded oligonucleotide, at least one nucleotide is a nucleotide X, and at least one nucleotide is a fluoro modified nucleotide; and in a 5' to 3' direction, the 13th nucleotide is a substituted alkoxy modified nucleotide; the 14th nucleotide is a nucleotide X; and each of the 15th nucleotide and all the subsequent nucleotides independently of one another is a modified nucleotide; and each nucleotide X is independently a deoxyribonucleotide or an unmodified nucleotide. The present disclosure also provides a double-stranded oligonucleotide, an oligonucleotide conjugate and a pharmaceutical composition comprising the single-stranded oligonucleotide as an antisense strand.

The invention relates to oligonucleotide hydrogel and a preparation method and application thereof, and the preparation method comprises the following steps: sequentially adding oligonucleotide and a PBS buffer solution into a metal salt solution, and mixing to obtain a mixed solution; placing the mixed solution in a shaking table, and oscillating and incubating; after incubation, centrifuging, discarding the supernatant, and retaining the precipitate; adding deionized water to resuspend the precipitate, centrifuging, discarding the supernatant, and washing to obtain hydrogel; according to the method, only single-stranded oligonucleotide is needed, special requirements on oligonucleotide sequence composition and structure are not needed, special design is not needed, divalent and trivalent metal ions can be assembled with the hydrogel, the process is simple, operation is easy and convenient, biological enzyme can be wrapped in the hydrogel, and enzyme immobilization and recycling are achieved.

The invention discloses a nucleic acid composition, application thereof and a Parkinson's disease detection kit. The nucleic acid composition comprises: a single-stranded circular nucleic acid comprising a DNA sequence as shown in SEQ ID No.1; and a single-stranded oligonucleotide capable of complementarily hybridizing to the single-stranded cyclic nucleic acid and capable of specifically binding to a monomer or oligomer of alpha-synuclein. The nucleic acid composition can be applied to nanopore detection of the exclusion volume of the alpha-synuclein oligomer. The alpha S oligomers in different aggregation states in a sample can be specifically captured through a designed annular DNA frame structure, and due to the fact that unique via hole signals with sub-peaks are generated through capturing of the annular structure of the frame, quantitative measurement of the volume of the alpha S oligomers can be achieved through statistical analysis of the sub-peak signals. The invention can provide a new thought and strategy for early diagnosis of Parkinson's disease.

Disclosed herein are methods of purifying oligonucleotides, for example, by separating double-stranded oligonucleotides from single-stranded oligonucleotides. Also provided are apparatuses for performed such methods. Also provided are double-stranded nucleic acid compositions and single-stranded nucleic acid compositions made using the methods and apparatuses disclosed herein. Also provided are methods of producing circular double-stranded nucleic acids.