1388results about "Screening process" patented technology

The present disclosure provides systems and methods for processing or analyzing a sample. Methods may include generating supports (e.g., beads) comprising barcode molecules coupled thereto. A support comprising barcode molecules may be useful for analyzing or processing one or more analytes such as nucleic acid molecules, proteins, and / or perturbation agents.

Provided herein are gene editing pairs comprising an engineered protein, e.g, an engineered CRISPR protein and a guide ribonucleic acid (gRNA) that may provide improved gene editing relative to reference, i.e., wild type sequences. In some embodiments, the engineered protein of the gene editing pair comprises a RuvC cleavage domain with one or more amino acid modifications relative to a reference CRISPR protein RuvC sequence. In some embodiments, a guide ribonucleic acid (gRNA) of the gene editing pair comprises at least one modification in a scaffold stem loop relative to a reference scaffold stem loop sequence.

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.

A Class 2, Type VI clustered regularly interspaced short palindromic repeat (CRISPR) RNA (gRNA) which comprises a direct repeat (DR) stem loop sequence and a guide or spacer sequence, is provided. Also described are methods for generating, selecting, characterizing and optimizing a clustered regularly interspaced short palindromic repeats (CRISPR) RNA (gRNA) for use in the CRISPR-CaslSd system described herein. Also provided is a screening method to identify gRNA particularly suited for use with specified targets.

Provided herein are methods for treating conditions and disease characterized by SCN1A, SCN8A or SCN5A protein deficiency by targeting the alternative splicing events in the SCN1A gene and modulating the expression level of functional proteins in Dravet Syndrome patients and / or inhibit aberrant protein expression.

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 herein are polypeptides that bind to a transferrin receptor, methods of generating such polypeptides, and methods of using the polypeptides to target a composition to a transferrin receptor-expressing cell.

Aptamers as nucleic acid affinity reagents are gaining traction in analytical applications owing to their high stability, compact size, and amenability to chemical modifications. It is highly desired to generate aptamers with different binding affinities to meet the requirements of various applications. However, systematic evolution of ligands by exponential enrichment (SELEX), the gold standard for aptamer generation, is unable to quantitatively produce aptamers with desired binding affinities and requires multiple rounds of selection to eliminate false positive hits. Here we introduce Pro-SELEX, a new approach for rapid discovery of aptamers with precisely defined binding affinities that combines efficient particle display, high-performance microfluidic sorting and high-content bioinformatics. Using the Pro-SELEX workflow, we were able to investigate the binding performance of individual aptamer candidates under different selective pressure in a single round of selection. Using human myeloperoxidase (MPO) as a target, we demonstrated that aptamers with dissociation constants spanning a twenty-fold range of affinities can be identified within one round of Pro-SELEX. Our selection strategy will have a significant impact on the fields of biosensing and bioseparation by generating aptamers with tailored binding affinities.

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.

Compositions and methods useful to reduce expression of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) gene and for treatment of HMGCR-associated diseases and conditions. HMGCR dsRNA agents, HMGCR antisense polynucleotide agents, compositions comprising HMGCR dsRNA agents, and compositions comprising HMGCR antisense polynucleotide agents that can be used to reduce HMGCR expression in cells and subjects.

The present invention relates to the fields of therapy and drug delivery. More specifically, disclosed herein are therapeutic methods and pharmaceutical compositions for treating disorders of the central nervous system. The disclosed methods and compositions involve localised administration into such organs of an effector component that targets an intracellular biological target, in combination with a saponin component that enhances effective uptake of the effector component into the cells and / or that enhances effective routing of the effector component inside the cells where the biological target is present. For example, the effector component can be an oligonucleotide therapeutic that is targeting a gene product associated with the disorder of the CNS. Due to cellular uptake-stimulating and / or endosomal escape enhancing effects of the saponin component, the presented herein neuropharmaceutical compositions for the localised administration into the CNS can be formulated with lower concentrations of the effector component and / or at lower volumes, which confers safety-benefits to the neurons and to the comfort of the patient.

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.

The invention discloses CML and CEL aptamers screened based on an efficient microfluidic SELEX platform, and belongs to the technical field of food safety biology. Through the microfluidic SELEX platform integrated with library fixation, target and library incubation, magnetic separation, fluorescence monitoring and other functions, the capsule SELEX screening method with less magnetic bead consumption, higher library immobilization rate, shorter screening time and higher enrichment efficiency is realized; the requirements and limitation of methods such as qPCR (quantitative polymerase chain reaction) and fluorescence ratio determination on specific instruments in the prior art are broken through; finally, the aptamer S2 with excellent performance of CML and CEL is obtained for the first time through the screening method, truncation optimization is carried out based on the combination mechanism of the aptamer S2, the aptamer S2-40 with shorter sequence and more excellent performance is obtained, and the dissociation constants measured by an ITC method and an SGI method are 6.65 + / -3.07 mu M and 42.1 + / -19.34 nM.

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.