989results about "Screening process" patented technology

A dual-targeting siRNA agent, comprising two different siRNAs targeting two different genes or pharmaceutically acceptable salts thereof, the two different siRNAs or salts thereof being linked to each other by means of a pharmaceutically acceptable ligand, the siRNAs being dsRNAs consisting of sense strands and antisense strands, and the two different genes being two selected from angiotensinogen (AGT), proprotein convertase subtilisin / kexin type 9 (PCSK9) and human angiopoietin-like protein 3 (ANGPTL3). Also provided is the use of the dual-targeting siRNA agent in preparing a drug for preventing or treating diseases related to hypertension or / and lipid imbalance. The dual-targeting siRNA agent can simultaneously and effectively inhibit the expressions of the two target genes in vivo, and has the advantages of no mutual antagonism, high activity and high safety. Further provided are siRNAs of genes corresponding to the dual-targeting siRNA agent and the use thereof for preventing or treating diseases related to hypertension or / and lipid imbalance.

The specification provides methods for introducing a desired genetic change in a nucleotide sequence using a double-strand break (DSB)-inducing genome editing system, the method comprising: identifying one or more available cut sites in a nucleotide sequence; analyzing the nucleotide sequence and available cut sites with a computational model to identify the optimal cut site for introducing the desired genetic change into the nucleotide sequence; and contacting the nucleotide sequence with a DSB-inducing genome editing system, thereby introducing the desired genetic change in the nucleotide sequence at the cut site.

Provided are an INHBE gene-targeted double-stranded oligonucleotide, a conjugate, and a composition, which relate to the technical field of nucleic acid drugs. The double-stranded oligonucleotide comprises a sense strand and an antisense strand. The antisense strand is complementary or substantially complementary to the sense strand; the sense strand comprises a nucleotide sequence identical or substantially identical to at least 15 consecutive nucleotides in a sequence of SEQ ID NO: 309, and said substantially identical means that there is no more than three nucleotide differences between the sense strand and the at least 15 consecutive nucleotides in the sequence of SEQ ID NO: 309. The double-stranded oligonucleotide can effectively inhibit the INHBE gene and treat patients suffering from metabolic diseases or metabolic syndrome and related diseases such as diabetes, hypertension and cardiovascular diseases.

Agents that target a processed mRNA, e.g., the 5′ UTR of the processed mRNA, can modulate protein expression, e.g., via modulation of translation of the processed mRNA. Alternative splicing events in genes can lead to non-productive mRNA transcripts which in turn can lead to aberrant protein expression. Agents that target the alternative splicing events in genes can modulate the expression level of proteins. Therapeutic agents, which can modulate protein expression by targeting a processed mRNA and / or alternative splicing events, can promote functional protein expression in patients and / or inhibit aberrant protein expression. Such therapeutic agents can be used to treat a condition or disease associated with protein deficiency and / or mitochondrial function deficit.

The invention discloses a method for detecting a diallele editing cell based on a CRISPR / Cas12a technology. The invention provides crRNA, and the nucleotide sequence of a binding target of the crRNA is SEQ ID NO.6. The crRNA is obtained by in-vitro transcription of a transcription template; the transcription template is a product obtained by annealing a single-stranded DNA (Deoxyribose Nucleic Acid) molecule as shown in SEQ ID NO.10 and a single-stranded DNA molecule as shown in SEQ ID NO.13. The invention provides crRNA of the CD71 gene, a CRISPR / Cas12a system is constructed by using the crRNA, CRISPR / Cas12a detection is performed, screening of CRISPR / Cas9 induced CD71 gene diallele editing cells is realized, and the method is simple, convenient, quick and convenient for economically and effectively screening a large number of mutant cells.

Provided are a double-stranded RNA targeting coagulation factor XI, a pharmaceutically acceptable salt thereof, or a ligand conjugate thereof。 Further provided are a pharmaceutical composition comprising the double-stranded RNA, the pharmaceutically acceptable salt thereof, or the ligand conjugate thereof, as well as a therapeutic use of the double-stranded RNA, the pharmaceutically acceptable salt thereof, or the ligand conjugate thereof.

This disclosure relates to oligonucleotides, compositions and methods useful for reducing SLC6A19 mRNA and / or B0AT1 protein expression, particularly in kidney cells. Disclosed oligonucleotides for the reduction of SLC6A19 / B0AT1 expression may be double-stranded or single-stranded and may be modified for improved characteristics such as stronger resistance to nucleases and lower immunogenicity. Disclosed oligonucleotides for the reduction of SLC6A19 / B0AT1 expression may also include targeting ligands to target a particular cell or organ, such as the proximal tubular epithelial cells and podocytes of the kidney, and may be used to treat diseases or disorders, including renal diseases and disorders (e.g., PKU, urea cycle disorders, chronic kidney disease, renal tubular acidosis, etc.).

The present disclosure provides compositions for targeting trans-splicing of an mRNA precursor in a cell and methods of using the same.

Compositions and methods useful to reduce expression of INHBE gene and for treatment of INHBE-associated diseases and conditions are provided. Provided are INHBE dsRNA agents, INHBE antisense polynucleotide agents, compositions comprising INHBE dsRNA agents, and compositions comprising INHBE antisense polynucleotide agents that can be used to reduce INHBE expression in cells and subjects.

Compositions comprising aptamers capable of specifically binding to a surface protein of Clostridium difficile spore are provided. A method for detecting, enriching, separating, and / or isolating Clostridium difficile spores is provided.

Cas-cleavable reporter systems, CRISPR-Cas systems thereof, and methods of use thereof in CRISPR-Cas based diagnostics. Cas-cleavable reporter systems may generate a luminescent, fluorescent, or other detectable signal upon Cas-collateral cleavage of one or more reporter system components. CRISPR-Cas systems may comprise a Cas protein having collateral cleavage activity, guide molecules, and the Cas-cleavable reporter system. Cas-cleavable reporter systems may be a split luciferase reporter system, at least one element of which is bound to beads. For multiplexing, CRISPR-Cas systems may comprise a Cas-cleavable quenched reporter system, optionally a Cas-cleavable quenched fluorescent reporter system, a Cas protein having collateral cleavage activity, and target-specific guide molecules attached to color-coded beads. CRISPR-Cas systems may further comprise amplification reagents. Methods may apply said CRISPR-Cas systems to flow cell, well-plate, or other devices, and may measure detectable signals by microscopic, plate reader, or other methods.

The present application relates to single-stranded or double-stranded interfering RNA molecules (e.g., siRNAs) that target the alpha synuclein (SNCA) gene. The interfering RNA molecule may contain a specific pattern of nucleoside modification and inter-nucleoside linkage modification as a pharmaceutical composition comprising the interfering RNA molecule. The siRNA molecule may be a branched siRNA molecule, such as a two-branched, three-branched or four-branched siRNA molecule. The disclosed siRNA molecules may also be characterized by a 5 '-phosphorus stabilizing moiety and / or a hydrophobic moiety. In addition, the present disclosure provides methods for delivering siRNA molecules of the present disclosure to a subject, such as the central nervous system of a subject identified as having synucleinopathies.

The present disclosure provides engineered immune cells modified to overexpress tumor sensing enhancer proteins, thereby providing the engineered immune cells with an enhanced ability to migrate to and / or infiltrate tumors. In some examples, the tumor sensing enhancer proteins are tumor sensing receptors that specifically bind to non-chemokine receptors. The disclosure also provides methods including the provided engineered immune cells.

Compositions and methods useful to reduce expression of sodium voltage-gated channel alpha subunit 9 (SCN9A) gene and for treatment of SCN9A-associated diseases and conditions are provided. Provided are SCN9A dsRNA agents, SCN9A antisense polynucleotide agents, compositions comprising SCN9A dsRNA agents, and compositions comprising SCN9A antisense polynucleotide agents that can be used to reduce SCN9A expression in cells and subjects.

Embodiments disclosed herein provide methods, including computer-implemented methods, for designing guide sequence which may be incorporated into custom, large scale guide sequence libraries. The methods require only a list of target genes as input and utilize on target and off target scores to generate an optimal set of guide sequences for a set of target genes. In certain embodiments, the methods may also utilize multi-tissue RNA-sequencing data and / or protein annotation to design targets to genes that are highly expressed and / or contain a functional protein domain. The invention further comprises guide libraries, cells comprising said guide libraries. Computer-implemented embodiments further improve computer system function by reducing excessive user wait time through the use of data structures that reduce search from linear to logarithmic time.

Because alternative splicing events in the SCN1A gene can result in non-productive mRNA transcripts, which can then lead to abnormal protein expression, therapeutic agents that can target alternative splicing events in the SCN1A gene can regulate the expression level of functional protein and / or inhibit abnormal protein expression in Dravet syndrome patients. Such therapeutic agents can be used to treat conditions caused by SCN1A, SCN8A, or SCN5A protein deficiencies.

Compositions and methods useful to reduce expression of synuclein alpha (SNCA) gene and for treatment of SNCA-associated diseases and conditions are provided. Provided are SNCA dsRNA agents, compositions or cells comprising SNCA dsRNA agents, that can be used to reduce SNCA expression in cells and subjects.

Provided herein are nucleic acid inhibitors or activators that impact the expression, levels or activity of SNORA13 in a cell. Also provided are pharmaceutical compositions for using these activators and inhibitors for the treatment of ribosomopathies, cancer, and senescence-associated pathologies.

The object of the present invention is an aptamer capable of specific detection of manganese ions which has a nucleotides sequence described in SEQ. ID NO. 1. An aptasensor with affinity to manganese ions Mn2+ which comprises a gold working electrode (1) coated with a receptor layer (2) comprising aptamers (3) and filler (4) molecules and an anionic indicator (5) that is present in the solution. A method of obtaining aptasensor comprising a step of forming the receptor layer (2) by incubation of the gold electrodes (1) in an aptamer (3) solution for 2 h and step b) of incubation with a filler (4) solution for 1 h to eliminate non- specific interactions on the surface of the electrode. The use of the aptamers as a receptor layer of a biosensor for selective in situ detection of manganese ions by electrochemical techniques.

This disclosure relates to isolated oligonucleotides comprising duplex regions targeting human LPA mRNA, and delivery systems, kits and compositions comprising the same, and methods of using the same for inhibiting or downregulating Lp(a) gene expression.

Disclosed is a virus-like particle capable of self-assembling in a host cell and encapsulating or encompassing a cargo. And the structural protein contributes to the overall structure of the virus-like particle, that does not comprise a nucleocapsid (NC) domain.

The present disclosure provides in one aspect a method of enhancing an immune response in a subject in need thereof. In certain embodiments, the method comprises administering to the subject an effective amount of a gene silencing system comprising a plurality of gRNAs, wherein the gene silencing system decreases expression of at least one endogenous immunosuppressive gene in a target cell, thereby enhancing the immune response. Also included are methods and compositions for enhancing anti-tumor immune responses in subject in need thereof.

Provided in some aspects are epigenetic-modifying DNA-targeting systems, such as CRISPR-Cas / guide RNA systems, that bind to or target a target site in a gene or regulatory element thereof in a T cell. In some aspects, the provided epigenetic modifying DNA-targeting systems provided herein modulate a T cell phenotype or activity. In particular, the provided embodiments relate to the transcriptional repression of genes to promote a stem cell-like memory T (TSCM) cell phenotype. In some aspects, also provided are compositions, polynucleotides, vectors, cells, and pluralities and combinations thereof, and methods and uses related to the provided epigenetic-modifying DNA-targeting systems, for example in modulating the phenotype in T cells including in connection with adoptive T cell therapy.

The present disclosure provides a modified oligonucleotide sequence and its application. A series of siRNAs are designed based on the angiotensinogen (AGT) messenger ribonucleic acid (mRNA) sequence, and are alternately modified and modified using a specific set of modification templates. The results of cell and animal experiments show that some alternately modified and specifically template-modified oligonucleotide sequences can significantly inhibit the expression of the AGT gene, and can be used for developing drugs for treating related diseases such as hypertension.

The present invention relates to methods and compositions for editing a polynucleotide, e.g., a polynucleotide comprising a SNP associated with a disease or disorder.

In one aspect, the present disclosure provides a method for identifying treatment targets relating to tumors. In another aspect, the present disclosure provides a method for identifying biomarkers and molecular features of normal and cancer cells.

Aptamer-based switch technology provides enhanced control over the use of chimeric antigen receptor (CAR)-associated immunotherapies. Aptamer-based switches utilize synthetic bridge molecules containing a target-binding aptamer linked to a CAR-binding aptamer via a linker. Systems containing a CAR and a corresponding aptamer bridge can (i) target any desired antigen by selecting the target-binding aptamer of the bridge; (ii) redirect from one target to another by changing the target-binding aptamer; (iii) be administered according to the changing needs of an individual patient over time by changing the administration protocol of the bridge; (iv) be switched on or off rapidly or gradually; (v) be used as a companion diagnostic for a specific CAR therapy; (vi) be integrated with in vitro or in vivo CAR expression; (vii) be non-immunogenic; and (viii) provide an immunotherapy platform with low production costs.