39 results about "Single stranded oligonucleotides" patented technology

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.

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 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.

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.

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.

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 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.

Compositions and methods are provided for forming a single RNA polynucleotide from a plurality of DNA oligonucleotides in a single reaction chamber using combined reagents in a single step reaction. DNA polymerase, RNA polymerase and single stranded (ss) DNA oligonucleotides are combined where each DNA oligonucleotide has one or more sequence modules, wherein one sequence module in the first ss DNA oligonucleotide is complementary to a sequence module at the 3′ end of the second ss DNA oligonucleotide; and wherein a second module on the first ss DNA oligonucleotide is an RNA polymerase promoter sequence; and forming a single RNA polynucleotide, excluding the RNA promoter sequence, derived from the first and second DNA oligonucleotides.

Disclosed herein are compositions and methods for detecting target sites in proximity to each other. Disclosed herein is a composition comprising; A) a first detection molecule conjugated to a first single stranded oligonucleotide tag, wherein the first detection molecule binds a first target site; B) a second detection molecule conjugated to a second single stranded oligonucleotide tag, wherein the second detection molecule binds a second target site; and C) a first proximity connection agent (PCA), wherein the first PCA comprises: i) a first nucleic acid sequence that hybridizes to the first single stranded oligonucleotide tag; and ii) a second nucleic acid sequence that hybridizes to the second single stranded oligonucleotide tag; wherein the first nucleic acid sequence hybridizes to the first single stranded oligonucleotide tag and the second nucleic acid sequence hybridizes to the second single stranded oligonucleotide tags when the first and second target sites are in proximity.

A single-stranded oligonucleotide, having a length of 16-30 nucleotides, the composition of the single-stranded oligonucleotide enabling the single-stranded oligonucleotide to inhibit the expression of NTCP mRNA by means of an RNAi mechanism. Each nucleotide in the single-stranded oligonucleotide is independently a modified or unmodified nucleotide. In the single-stranded oligonucleotide, at least one nucleotide is nucleotide X, and at least one nucleotide is a fluoro-modified nucleotide. In the direction from the 5' end to the 3' end, the 13th nucleotide of the single-stranded oligonucleotide is a substituted alkoxy-modified nucleotide, the 14th nucleotide of the single-stranded oligonucleotide is nucleotide X, and the 15th nucleotide and all the following nucleotides of the single-stranded oligonucleotide are each independently a modified nucleotide. Also provided are a double-stranded oligonucleotide including 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 and APOE4 mRNA have complementarity sufficient to mediate an RNAi effect; and each nucleotide in the single-stranded oligonucleotide is a modified or unmodified nucleotide. Also provided are a double-stranded oligonucleotide comprising the single-stranded oligonucleotide as an antisense strand, an oligonucleotide conjugate, and a pharmaceutical composition.

A single-stranded oligonucleotide. Each nucleotide in the single-stranded oligonucleotide is independently a modified or unmodified nucleotide, wherein the single-stranded oligonucleotide has a length and composition that enable the single-stranded oligonucleotide to inhibit the expression of PSD3 mRNA in animals by means of an RNAi mechanism. Disclosed are a double-stranded oligonucleotide comprising the single-stranded oligonucleotide as an antisense strand, an oligonucleotide conjugate, and a pharmaceutical composition.

One aspect of the present invention relates to a single-stranded oligonucleotide having a sequence represented by formula (II) or (III): (5'-Z 11 -3')-L-Q S -(5'-Z 12 -3')(II), (3'-Z 11 -5')-L-Q S -(3'-Z 12 -5')(III). In formula (II) or (III), Z 11 is a first oligonucleotide comprising 15 to 100 optionally modified nucleotides that is substantially complementary to the target gene; Z 12 is a second oligonucleotide comprising 10 to 100 optionally modified nucleotides that is substantially complementary to Z 11 ; Z 11 and Z 12 can form an intrastrand double-stranded region containing 7 or more consecutive base pairs; Q S represents 0 to 12 optionally modified nucleotides; L is an arbitrary linking group; at least one nucleotide of formula (II) is a modified nucleotide; at least one nucleotide of formula (III) is a modified nucleotide; at least one nucleotide at the 3'-end of Z 11 in formula (II), or at least one nucleotide at the 5'-end of Z 11 in formula (III), in either case together with L and Q S forms a loop region connecting Z 11 and Z 12 .

The invention relates to methods and systems for gene editing combining endonuclease mediated homology directed repair using single stranded oligonucleotides templates with a site-specific recombinase to allow large cargos to be integrated at any location in the genome.

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, one of the numerous binding sites has a dimension of about 1 micrometer to about 20 micrometers, each of the numerous binding sites comprises a plurality of single-stranded oligonucleotides, and the plurality of single-stranded oligonucleotides is coupled to the planar surface.wherein 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.