505 results about "Sense strand" patented technology

A modification template for improving the inhibitory effect of a double-stranded oligonucleotide on a target gene, a combination thereof and the use thereof. The double-stranded oligonucleotide is an siRNA and contains a sense strand and an antisense strand, and each nucleotide of the sense strand and antisense strand is a modified nucleotide. The double-stranded oligonucleotide is modified with a special modification template, and has a significantly improved inhibition rate on a target gene compared with a basic sequence.

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.

The invention discloses a modification template for improving the target gene inhibition effect of double-stranded oligonucleotide and a combination and application of the modification template, the double-stranded oligonucleotide is siRNA and contains a positive-sense strand and an antisense strand, and each nucleotide of the positive-sense strand and the antisense strand is a modified nucleotide. The double-stranded oligonucleotide is modified by a special modification template, and compared with a basic sequence, the inhibition rate of the double-stranded oligonucleotide to a target gene is remarkably improved.

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.

Relating to the technical field of gene therapy, provided is an siRNA molecule for inhibiting PCSK9 expression, and use thereof. Particularly, an siRNA molecule for inhibiting PCSK9 expression (comprising a sense strand and an anti-sense strand that are complementary to form a double-stranded region) and a pharmaceutical composition comprising the same are disclosed. The siRNA molecule has a high silencing efficiency and a long-lasting silencing effect for PCSK9 gene, and is useful in the manufacture of products for inhibiting PCSK9 protein expression, products for reducing the concentration of low-density lipoprotein or low-density lipoprotein cholesterol in serum; and products for relieving the symptoms of PCSK9 gene-mediated diseases.

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.

A nucleic acid molecule comprising: i) a first nucleic acid comprising a double stranded inhibitory ribonucleic acid (RNA) molecule comprising a sense and an antisense strand designed with reference to a nucleotide sequence comprising a cardiovascular disease associated gene to be silenced and wherein said cardiovascular gene is proprotein convertase subtilisin kexin 9 (PCSK9) there is provided a single stranded deoxyribonucleic acid (DNA) molecule conjugated to the 5’ end of said sense strand; and ii) a second nucleic acid comprising a double stranded inhibitory ribonucleic acid (RNA) molecule comprising a sense and an antisense strand designed with reference to a different cardiovascular disease associated gene to be silenced wherein said cardiovascular gene is lipoprotein (a) (Lp(a)) and wherein there is provided a single stranded deoxyribonucleic acid (DNA) molecule conjugated to the 5’ end of said sense strand wherein the single stranded deoxyribonucleic acid (DNA) molecule is substantially complementary to the single stranded deoxyribonucleic acid (DNA) molecule set forth in i) above and anneals by complementary base pairing to form a double stranded DNA linker that links the first and second double stranded inhibitory ribonucleic acid (RNA) molecules.

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 provides siRNA for targeted regulation and control of HBV gene expression and application of the siRNA. The double-stranded RNAi agent comprises an antisense strand and a sense strand complementary to the antisense strand forming a double-stranded region, and the nucleotide sequence of the antisense strand is as shown in SEQ ID NO: 8, or the nucleotide sequence of the antisense strand is a modified sequence of the sequence as shown in SEQ ID NO: 8. Cell and animal experiment results show that the double-stranded RNAi agent provided by the invention can significantly reduce the expression of one or more HBV genes and block the life cycle of viruses, and can be used for developing drugs for treating HBV gene expression related diseases.

The disclosure provides, for example, a double stranded DNA (dsDNA) molecule comprising chemically modified nucleotides. In some embodiments, the dsDNA molecule comprises an upstream DNA end form which is a closed end, a downstream DNA end form which is a closed end, and a double stranded region comprising a sense strand and an antisense strand, in which the sense strand comprises one or more chemically modified nucleobases, and the antisense strand is free of chemically modified nucleobases.

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.

Provided siRNA for inhibiting XDH gene expression and a modifier and use thereof. The siRNA comprises a sense strand and an antisense strand. The sense strand and / or the antisense strand have a length in the range of 19-25 nucleotides, and the antisense strand is reversely complementary to a segment on a target gene; and the sense strand has a nucleotide sequence as shown in SEQ ID NO: 1-14, and the antisense strand has a nucleotide sequence as shown in SEQ ID NO: 18-31. siRNA molecules and modified siRNA molecules have high stability and / or high inhibitory activity. Ligand-conjugated siRNA molecules have good liver targeting performance and the capability to promote cell endocytosis while maintaining high inhibitory activity and stability, can reduce the impact on other tissues or organs and reduce the amount of siRNA molecules used, and can achieve the purposes of reducing toxicity and reducing costs.

The present disclosure provides a siRNA for inhibiting the expression of apolipoprotein C3 (ApoC3) gene, and a pharmaceutical composition and a conjugate comprising the siRNA; wherein each nucleotide in the siRNA is independently a modified 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 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.

Provided is novel siRNA having an RNA interfering action and / or a gene expression suppressing action on mRNA encoding TfR2, or the like. An oligonucleotide or a pharmaceutically acceptable salt thereof, or the like, has a knockdown action on mRNA of transferrin receptor 2, and consists of an antisense strand region containing a target-matching sequence substantially complementary to a target sequence in mRNA encoding TfR2, and a sense strand region containing a nucleotide sequence substantially complementary to the target-matching sequence of the antisense strand region.

Provided is an siRNA for inhibiting the gene expression of complement factor B (CFB), or a pharmaceutical composition or conjugate containing the siRNA. The siRNA contains a sense strand and an antisense strand. Each nucleotide in the siRNA is an independent modified or unmodified nucleotide. The sense strand contains a segment of nucleotide sequence I, and the nucleotide sequence I and a nucleotide sequence show in SEQ ID NO: 1 have an equal length and differ by no more than 3 bases. The antisense strand contains a nucleotide sequence II, and the nucleotide sequence II and a nucleotide sequence shown in SEQ ID NO: 2 have an equal length and differ by no more than 3 bases. The siRNA or the pharmaceutical composition or conjugate containing the siRNA can effectively treat and / or prevent diseases related to the mRNA level of the gene expression of the CFB.

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.

A double-stranded siRNA for inhibiting PNPLA3 expression and a conjugate comprising same. The double-stranded siRNA comprises a sense strand and an antisense strand, wherein one or more nucleotide residues in a nucleotide sequence of the sense strand and / or the antisense strand are replaced with r1 represented by formula I: formula (I). The introduction of a non-natural nucleotide monomer into the double-stranded siRNA improves the target selectivity and activity of the siRNA sequence, reducing the off-target risk while maintaining high drug activity. Also provided is a tetravalent GalNAc, making it easier to scale up synthesis and reduce costs.

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 belongs to the technical field of gene engineering, and discloses a preparation method and application of small-fragment DNA and the small-fragment DNA. According to the preparation method of the small-fragment DNA, provided by the invention, a forward fragment group and a reverse primer group which are obtained by carrying out segmentation design on a positive-sense strand and an antisense strand of the small-fragment DNA are used for replacing primers and template DNA which are conventionally used in existing PCR amplification, and the capability of forming a dimer between a forward fragment fragment and a reverse fragment fragment is ingeniously utilized; a PCR amplification reaction system contains a complete nucleotide sequence required by amplification to obtain small-fragment DNA, and a dimer formed by a forward fragment fragment and a reverse fragment fragment has a free fragment and can extend in a PCR amplification cycle so as to gradually form the complete small-fragment DNA, so that the small-fragment DNA can be obtained. The method can effectively overcome the limitation on the design of the primer caused by the short DNA length of the small fragment in the existing PCR amplification method, can quickly, efficiently and accurately amplify the DNA of the small fragment, and has a good application prospect in the genetic engineering technology.

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.

The invention relates to the technical field of biological medicine, and particularly discloses siRNA of a targeted RIG-I receptor gene and application of the siRNA, the siRNA is selected from any one of siRNA-1 and siRNA-3, the siRNA-1 comprises a positive-sense strand with the nucleotide sequence shown as SEQ ID NO.1 and an antisense strand with the nucleotide sequence shown as SEQ ID NO.2, and the siRNA comprises a positive-sense strand with the nucleotide sequence shown as SEQ ID NO.1 and a negative-sense strand with the nucleotide sequence shown as SEQ ID NO.2. The siRNA-3 comprises a positive-sense strand of which the nucleotide sequence is as shown in SEQ ID NO.5 and an antisense strand of which the nucleotide sequence is as shown in SEQ ID NO.6. The invention further discloses a preparation method of the siRNA-3. The siRNA provided by the invention is used for inhibiting expression of RIG-I receptor genes so as to reduce inflammatory response in a dairy cow mammary epithelial cell inflammation model, so that the siRNA provided by the invention can be used for preparing the medicine for treating dairy cow mastitis.

The invention belongs to the field of biological medicine, and relates to siRNA and a conjugate for inhibiting APP gene expression, the siRNA comprises a positive-sense strand and an antisense strand, the positive-sense strand comprises a nucleotide sequence I, and the antisense strand comprises a nucleotide sequence II; each nucleotide in the nucleotide sequence I and the nucleotide sequence II is modified or unmodified nucleotide; the nucleotide sequence I and the nucleotide sequence II are at least partially reversely complementary to form a double-stranded region; the nucleotide sequence I is basically consistent with a first section of nucleotide sequence, and the first section of nucleotide sequence is a section of nucleotide sequence with the length of at least 19 nucleotides in mRNA expressed by an APP gene. The siRNA can specifically induce degradation of APP mRNA, so that synthesis of APP in the liver is inhibited, APP protein is induced to be reduced durably, pathological deposition of Abeta and other related toxic proteins is reduced, and the siRNA has a good patent medicine prospect.

To provide a metabolically stable phosphorothioate-modified RNA.SOLUTION: The present invention provides a modified oligonucleotide, having a 5' end and a 3' end, and comprising a sense strand and an antisense strand complementary to a target, and at least one modified intersubunit linkage of Formula I, where at least one modified oligonucleotide is incorporated into the antisense strand or sense strand of an siRNA.SELECTED DRAWING: None