407 results about "Sense strand" patented technology

The present invention discloses a pharmaceutical composition comprising a circular RNA and a drug delivery carrier. Compared with traditional linear 1 * siRNA and annular 1 * siRNA, the number of repeated series connection of positive-sense strands is increased to include but not limited to two or more, it is accidentally found that the silence effect is remarkably enhanced, the expression level of the PCSK9 gene can be remarkably reduced, and degradation of mRNA of PCSK9 protein is mediated. The nano-particles are used for delivering oligonucleotide, so that the stability is improved, the immunogenicity is reduced, the effects of lowering cholesterol, reducing aortic plaque load and resisting atherosclerosis are improved, and the nano-particles are safe and free of obvious liver and kidney toxicity and have a wide application prospect in the aspect of preparing medicines for treating hypercholesterolemia and coronary heart disease.

Provided is a circular multimeric tandem RNA sense strand, comprising at least one sense strand sequence and at least one spacer sequence. The circular RNA is derived from an engineered parental DNA template containing all essential sequences, and sequentially comprises a first cyclization element, optionally at least one first restriction enzyme recognition sequence, at least one target sequence, optionally at least one second restriction enzyme recognition sequence, and a second cyclization element. The circular multimeric tandem RNA sense strand can bind and deliver a plurality of antisense strand RNA, increasing the binding of the sense strand and the antisense strand while utilizing the stability advantage of circular RNA.

The invention provides annular multi-tandem PCSK9 siRNA, which comprises at least one positive-sense strand sequence and at least one spacer sequence. The sense strand of the cyclic siRNA is derived from an engineered parent DNA template containing all essential sequences, comprising in the following order a first cyclization element, optionally at least one first restriction enzyme recognition sequence, at least one target sequence, optionally at least one second restriction enzyme recognition sequence, and a second cyclization element. The annular multi-tandem RNA positive-sense strand can combine and deliver a plurality of antisense strand RNAs, and the combination of the positive-sense strand and the antisense strand is increased while the stability advantage of the annular RNA is utilized.

Provided is a pharmaceutical composition, comprising a circular RNA and a drug delivery carrier. It is surprisingly found that compared with conventional linear 1 x siRNAs and circular 1 x siRNAs, increasing the number of tandem repeats in the sense strand to two or more significantly enhances the silencing effect, significantly reduces the expression level of the PCSK9 gene, and mediates the degradation of the PCSK9 protein mRNA. The use of nano-particles for delivering oligonucleotides features improved stability, reduced immunogenicity, improved cholesterol-lowering, aortic plaque load-reducing and anti-atherosclerotic effects, good safety, no significant liver and kidney toxicity, and therefore good prospects in preparing medicaments for treating hypercholesterolemia and a coronary heart disease.

Provided is a circular concatemeric PCSK9 siRNA, comprising at least one sense strand sequence and at least one spacer sequence. The sense strand of the circular siRNA is derived from an engineered parental DNA template containing all essential sequences, which comprises, in the following order: a first cyclization element, optionally at least one first restriction enzyme recognition sequence, at least one target sequence, optionally at least one second restriction enzyme recognition sequence, and a second cyclization element. The sense strand of the circular concatemeric RNA can bind and deliver a plurality of antisense strand RNAs, enhancing the binding between the sense and antisense strands while leveraging the stability advantage of the circular RNA.

The invention belongs to the technical field of gene engineering, and provides shRNA (short hairpin Ribonucleic Acid) for knocking down BST2 gene expression, a recombinant vector and application of the shRNA, and the shRNA comprises Bst2-shRNA-1 or Bst2-shRNA-2; the Bst2-shRNA-1 comprises a positive-sense strand of which the nucleotide sequence is as shown in SEQ ID NO. 1 and an antisense strand of which the nucleotide sequence is as shown in SEQ ID NO. 2; the Bst2-shRNA-2 comprises a positive-sense strand of which the nucleotide sequence is as shown in SEQ ID NO. 3 and an antisense strand of which the nucleotide sequence is as shown in SEQ ID NO. 4. The shRNA disclosed by the invention plays an important role in inhibiting non-infectious aseptic inflammation, can effectively delay the ALS attack time and protect motor neurons, has a very good application prospect, and also provides a direction and a technical basis for searching, researching and developing new therapeutic drugs for treating ALS.

The invention discloses siRNA for inhibiting GPR75 gene expression and application of the siRNA. The siRNA comprises a positive-sense strand and an antisense strand, and the antisense strand has a nucleotide sequence which is different from a nucleotide sequence shown in any one of SEQ ID NO.109-216 and SEQ ID NO.226-231 by not more than 3 nucleotides; the antisense strand and the positive-sense strand are at least partially complementary to form a double-strand region. The invention provides siRNA for inhibiting GPR75 gene expression, the siRNA is modified to ensure the stability and inhibitory activity of the siRNA, and experiments prove that multiple groups of siRNA have obvious inhibitory activity on GPR75 gene expression, and show application prospects in preparation of drugs for treating or preventing GPR75 expression related diseases in human bodies.

The invention discloses a molecular marker related to chicken slaughter traits and a new slaughter processing strain breeding method, and belongs to the technical field of gene detection. The SNP molecular marker corresponds to the 7132158 site of a positive-sense strand of a chromosome 5 of chicken reference genome Galusgallus-7.0 version sequence information published in NCBI (National Center of Biotechnology Information), and a basic group at the site is C or T. The SNP molecular marker is related to chicken slaughter traits, early selection is performed on the chicken slaughter traits by determining the genotype of the chicken SNP site to be detected, production cost can be saved, genetic progress can be accelerated, chicken breeding can be better served, and the SNP molecular marker has great economic application value and scientific research value.

This disclosure relates to an siRNA-lipid conjugate of formula Y-L-(H)n. Y is an siRNA molecule. L is a linker covalently bonded to Y and H, each H is independently a hydrophobic chain comprising 5 to 50 carbon atoms, n is 1, 2, or 3, and linker L is bonded to the 3′ end of the sense strand of the siRNA.

This disclosure relates to an siRNA-lipid conjugate of formula Y-L-(H)n. Y is an siRNA molecule, L is a linker covalently bonded to Y and H, each H is independently a hydrophobic chain comprising 5 to 50 carbon atoms, n is 1, 2, or 3, and linker L is bonded to the 3′ end of the sense strand of the siRNA.

The invention discloses a verticillium dahliae virulence gene, a verticillium dahliae virulence protein and application. The invention relates to the technical field of biology, and provides a method for preventing and treating cotton verticillium wilt based on RNAi (RNA interference) as well as related components and application thereof. Specifically, the invention discloses application of the verticillium wilt prevention and treatment by a method for inhibiting or silencing the expression of verticillium dahliae pathogenic gene VdHDAC (coding protein of the verticillium dahliae pathogenic gene VdHDAC is shown as SEQ ID NO: 3), the core of the verticillium wihliae pathogenic gene VdHDAC is to provide dsRNA molecules capable of targeting the gene, and the positive-sense strand of the dsRNA molecules is preferably selected from SEQ ID NO: 5, SEQ ID NO: 8, SEQ ID NO: 9 or SEQ ID NO: 11. Based on the molecule, the invention further provides a recombinant vector containing the coding sequence, a recombinant microorganism, a transgenic disease-resistant plant and an RNAi pesticide preparation. The scheme can be realized through host-induced gene silencing, microorganism-mediated gene silencing or preparation treatment and the like, the virulence of pathogenic bacteria can be effectively reduced, and a new technical approach is provided for green prevention and control of verticillium wilt.

Provided herein are, inter alia, agents (e.g., RNAi agents, dsRNA agents) comprising a sense strand and an antisense strand targeting CIDEB (e.g., hCIDEB); and methods of manufacturing and pharmaceutical compositions comprising the same. Further provided herein are methods of utilizing the agents (e.g., RNAi agents, dsRNA agents) including, e.g., methods of inhibiting or decreasing CIDEB expression (e.g., mRNA expression), methods of treating CIDEB associated diseases, and methods of treating liver diseases (e.g., MASH).

The invention discloses shRNA (short hairpin Ribonucleic Acid) for targeted knockout of an Eif2ak2 gene and application, and belongs to the technical field of gene engineering. The shRNA comprises a positive-sense strand and an antisense strand which is reversely complementary with the positive-sense strand, and the nucleotide sequence of the positive-sense strand is shown as SEQ ID NO. 5. It is found for the first time that the recombinant adeno-associated virus capable of inhibiting Eif2ak2 gene expression can successfully inhibit the phenotype of the abdominal aortic aneurysm of a mouse, obviously reduce the morbidity of the abdominal aortic aneurysm of the mouse, improve the severity of the abdominal aortic aneurysm of the mouse, reduce the inner diameter of a blood vessel and the ratio of the weight to the body weight of the blood vessel, and promote the contraction function of vascular smooth muscle cells of the mouse; the method can be used for effectively treating the abdominal aortic aneurysm, provides a new thought and strategy for treating the abdominal aortic aneurysm, and has a wide clinical application prospect.

The present invention relates to an siRNA for inhibiting FXI gene expression, an siRNA conjugate, a pharmaceutical composition containing same, and the use thereof. Each nucleotide in the siRNA is independently a modified or unmodified nucleotide, and the siRNA contains a sense strand and an antisense strand. The siRNA and the conjugate and pharmaceutical composition thereof can effectively treat and / or prevent diseases associated with FXI gene overexpression.

The invention relates to a dsRNA insecticide for preventing and treating thrips and a preparation method of the dsRNA insecticide. Belongs to the field of biotechnology and agricultural application. The dsRNA insecticide for preventing and treating the thrips is a preparation taking dsRNA as an effective component, and the dsRNA is of a double-stranded RNA structure containing a positive-sense strand and an antisense strand; the nucleotide sequence of the positive-sense strand is as shown in SEQ ID NO. 1, SEQ ID NO. 3, SEQ ID NO. 5, SEQ ID NO. 7, SEQ ID NO. 9 or SEQ ID NO. 11. The invention proves that dsACT and dsVATB can cause degradation of messenger RNA (Ribonucleic Acid) of ATP (Adenosine Triphosphate) enzyme coding genes in thrips and reduce the expression level of related genes; laboratory test and field efficacy test results jointly show that after the dsRNA insecticide is sprayed, the growth and development of the thrips are affected, individual death is further caused, and the achievement lays a good theoretical and application foundation for prevention and treatment of the thrips.

This vector for nucleic acid introduction contains a nucleotide sequence that encodes a Cas protein, a nucleotide sequence that encodes a guide RNA, and a nucleotide sequence of a nucleic acid to be introduced. The guide RNA targets an intron adjacent to the 5' side, with reference to a sense strand, of an exon that includes a stop codon. Also provided is a nucleic acid introduction method comprising a step for introducing a nucleic acid to be introduced through non-homologous end joining by targeting an intron that is adjacent to the 5' side, with reference to a sense strand, of an exon that includes a stop codon.

The present disclosure provides double stranded ribonucleic acid (dsRNA) agents for inhibiting expression of a target gene, comprising an antisense strand which is complementary to the target gene; a sense strand which is complementary to the antisense strand and forms a double stranded region with the antisense strand; at least one alpha-v-beta-6 (αvβ6) integrin targeting ligand that mediates delivery to muscle tissue conjugated to at least one strand; and at least one in vivo delivery enhancing moiety conjugated to one or more internal positions on at least one strand. The present disclosure also provides compositions comprising such dsRNA agents, and methods of use thereof for treating a subject having a disorder that would benefit from reduction in expression of the target gene.

The present invention belongs to the technical field of medicine and provides a carbocyclic nucleoside-containing siRNA conjugate, and a pharmaceutical composition and a use thereof. The sense strand and / or antisense strand of the siRNA conjugate comprises at least one carbocyclic nucleoside represented by structural formula (I) below. The sense strand comprises at least 16 consecutive nucleotides of the nucleotide sequence 5'-GUCAUCCACAAUGAGAGUACA-3', and the antisense strand comprises at least 18 consecutive nucleotides of the nucleotide sequence 5'-UGUACUCUCAUUGUGGAUGACGA-3'. The carbocyclic nucleoside-containing siRNA conjugate provided by the present invention can be used for treating, preventing, and / or alleviating AGT-related diseases, such as hypertension.

The invention discloses siRNA (small interfering Ribonucleic Acid) targeting TMEM86A and application thereof, and relates to the technical field of biology, the siRNA comprises the following positive-sense strands and antisense strands: siRNA-001: a positive-sense strand: 5 '-GAAGAGCGAAGGACCCAAATT-3'; according to the tumor-associated macrophage, TMEM86A has a positive-sense strand of 5 '-TTTGGGTCCTTCGCTTCT-3', an antisense strand of 5 '-TTTGGGTCCTGTCGCTTCT-3', siRNA-002 has a positive-sense strand of 5 '-GGCTCATGGTTCGGTTTT-3', and an antisense strand of 5 '-AAACCGAACCCATGAGCCT-3'. According to the tumor-associated macrophage, single cell sequencing analysis finds that TMEM86A is highly expressed in tumor-associated macrophages, and the development of tumors is inhibited by designing siRNA of TMEM86A to target the tumor-associated macrophages in a colon cancer tumor microenvironment.

An siRNA capable of inhibiting the expression of apolipoprotein C3 (APOC3) gene, comprising a sense strand and an antisense strand, wherein the sense strand and the antisense strand are respectively composed of nucleotide sequence I or nucleotide sequence II comprising 19 modified or unmodified nucleotides, and the nucleotide sequence I and the nucleotide sequence II are at least partially reverse complementary to form a double-stranded region, and the nucleotide sequence II is at least partially reverse complementary to a nucleotide sequence segment in the mRNA of APOC3 gene expression; in the direction from the 5'-end to the 3'-end, at least one of the 3-6th nucleotides of the nucleotide sequence II is a stabilized modified nucleotide. The siRNA as described above, as well as the pharmaceutical composition and siRNA conjugate comprising the siRNA, can effectively treat and / or prevent diseases or disorders related to APOC3 gene expression, and have a significantly reduced off-target effect.

To provide dsRNA molecules which are advantageous for inhibition of target gene expression while having reduced off-target gene silencing effects.SOLUTION: The present invention relates to double-stranded RNA (dsRNA) agent capable of inhibiting the expression of a target gene. The antisense strand of the dsRNA molecule comprises at least one thermally destabilizing nucleotide occurring at a seed region; the dsRNA comprises at least four 2'-fluoro modifications; and the sense strand of the dsRNA molecule comprises a ligand, where the ligand is an ASGPR ligand.SELECTED DRAWING: None

This invention discloses five RNAi molecules targeting the genome of the small cutworm, all of which are double-stranded RNA molecules composed of a sense strand and a complementary antisense strand, wherein the nucleotide sequence of the sense strand is selected from SEQ ID NOs:1-5. The lethality of these RNAi molecules against the small cutworm is all above 80%.

Double-stranded ribonucleic acid (dsRNAi) agents that target exon 1 of the huntingtin (HTT) gene are provided.SOLUTION: A double-stranded ribonucleic acid (dsRNA) agent for inhibiting the expression of huntingtin (HTT), the agent comprising a sense strand and an antisense strand forming a double-stranded region, wherein the sense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from a certain specific nucleotide sequence, and the antisense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from another certain specific nucleotide sequence, provided are dsRNA agents wherein one or more lipophilic moieties are conjugated to one or more internal positions on at least one of the sense or antisense strands.SELECTED DRAWING: None

The present disclosure relates to a nucleoside analogue and a use thereof. The nucleoside analogue is a compound shown in formula (Ia) or a prodrug thereof. The nucleoside analogue can enhance targeted delivery of oligonucleotide drugs to nervous system cells, thereby increasing the inhibition rate of the oligonucleotide drugs delivered in a targeted manner on expression of specific genes in the nervous system cells, or enabling the oligonucleotide drugs delivered in a targeted manner to achieve the purpose of preventing and / or treating pathological conditions or diseases caused by abnormal expression of the specific genes in the nervous system cells. The present disclosure also relates to a nucleotide analogue-containing double-stranded oligonucleotide and a use thereof. The double-stranded oligonucleotide comprises a sense strand and an antisense strand, each strand has 17-25 modified and / or unmodified nucleotides, and the antisense strand and the sense strand are complementary to form a duplex region; the sense strand and / or the antisense strand contains at least one nucleotide analogue represented by the structure of formula (100), or a tautomer, or stereoisomer, or pharmaceutically acceptable salt thereof; the double-stranded oligonucleotide can effectively treat and / or prevent pathological conditions or diseases caused by abnormal expression of specific genes in nervous system cells.

Provided are an siRNA targeting AZGP1 and the use thereof in the preparation of a drug for tumor treatment. An siRNA molecule for inhibiting the expression of an AZGP1 gene may be AZGP1-1, AZGP1-2, AZGP1-3, AZGP1-4, AZGP1-5, AZGP1-6 or AZGP1-7. The siRNA molecule comprises a sense strand and an antisense strand. The sense strand can be at least partially reverse complementary to the antisense strand to form a double-stranded region. The provided siRNA molecule targeting the AZGP1 gene can inhibit the invasion, proliferation and epithelial-mesenchymal transition of breast cancer cells, and is of great significance for treating cancer, especially breast cancer, by inhibiting the expression of the AZGP1 gene.

The invention discloses siRNA capable of knocking down Pr18a9 gene expression and application of the siRNA, and relates to the technical field of biological medicine. The invention provides a positive-sense strand sequence and an antisense strand sequence of the siRNA, and the siRNA is used for preparing a preparation for promoting Schwann cell survival. According to the invention, the Prl8a9 gene of SCs is knocked down by virtue of a small interfering RNA technology; by improving the proliferation and migration capabilities of the Schwann cells, the apoptosis rate of the Schwann cells is reduced, and the survival rate of the Schwann cells is further improved. Meanwhile, a transcriptome sequencing technology is applied, key genes and pathways of Schwann cells treated by siPr18a9 are deeply excavated, and a theoretical support is provided for research on a repair mechanism after peripheral nerve injury.

Provided are a siRNA for inhibiting the expression of an angiopoietin-like protein 3 (ANGPTL3) gene, and a pharmaceutical composition and a conjugate comprising the siRNA; wherein each nucleotide in the siRNA is independently a modified or unmodified nucleotide, and the siRNA comprises a sense strand and an antisense strand; the sense strand comprises a nucleotide sequence A, the nucleotide sequence A having the same length as the nucleotide sequence as represented by SEQ ID NO:1 with no more than 3 nucleotide differences; the antisense strand comprises a nucleotide sequence B, the nucleotide sequence B having the same length as the nucleotide sequence as represented by SEQ ID NO:2 with no more than 3 nucleotide differences.

The present invention provides an siRNA that inhibits angiopoietin-like 4 (ANGPTL4) gene expression, wherein the siRNA comprises a sense strand and an antisense strand, wherein the antisense strand comprises at least 17 continuous nucleotides that differ by no more than 4 nucleotides from the nucleotide sequences as shown in SEQ ID NO: 143, and the antisense strand is 17 to 30 nucleotides in length; the sense strand is 17 to 30 nucleotides in length and is at least partially complementary to the antisense strand. The siRNA, siRNA conjugate, and pharmaceutical composition provided in the present invention exhibit good stability, ANGPLT4 gene inhibitory activity, and immunostimulation, and can significantly reduce ANGPTL4 protein concentrations at the animal level.

Provided in the present invention are a siRNA for inhibiting the expression of complement component C5, the use thereof, and a product thereof, belonging to the technical field of small-molecule drugs and relating to the design and use of siRNA for C5 genes. The siRNA of the present invention comprises a sense strand and an antisense strand, wherein the sense strand comprises a nucleotide sequence as shown in SEQ ID NO. 1-SEQ ID NO. 546, and the antisense strand comprises a nucleotide sequence as shown in SEQ ID NO. 547-SEQ ID NO. 1092. Provided in the present invention is a brand new siRNA which can effectively inhibit the expression of complement component C5.

The present application relates to siRNA for inhibiting NR1H3 gene expression and its modification and conjugate and application, belong to the field of biotechnology. The present application provides a kind of siRNA for inhibiting NR1H3 gene expression, its sense strand includes the first nucleotide sequence as shown in any one of SEQ ID NO.4, SEQ ID NO.15, SEQ ID NO.33 or SEQ ID NO.74-SEQ ID NO.80, its antisense strand includes the second nucleotide sequence as shown in any one of SEQ ID NO.40, SEQ ID NO.51, SEQ ID NO.70 or SEQ ID NO.81-87. Experiments have confirmed that the siRNA of the present application and its modification and conjugate are all higher inhibitory activity to NR1H3, therefore, in the preparation of drug for treating disease related to lipid metabolism has very application prospect.