45 results about "Rna targeting" patented technology

Disclosed herein are Advanced RNA Targeting (ARNATAR) dsRNA compounds targeting Inhibin βE (INHBE). Such compounds are useful in methods for reducing expression of INHBE and for therapeutically treating INHBE associated diseases, disorders and / or conditions, or symptoms thereof in a subject.

The invention relates to the technical field of agricultural biology, in particular to application of a neuropeptide gene CpILP6 in relieving diapause of codling moths. After siRNA is microinjected to silence CpILP6 in a targeted manner, the diapause state of CpILP6 is changed and tends to a normal development phenotype; the research result of the invention provides a theoretical basis for defining the regulation function of the neuropeptide gene CpILP6 in the diapause induction and maintenance process of codling moth.

Disclosed are methods, systems, and computer readable media for predicting interactions for RNA sequences, including long noncoding RNA (IncRNA), which can be used, for example, as biomarkers. In an example method of predicting one or more binding sites between a ribonucleotide (RNA) sequence and a RNA binding protein, the method includes at a computing platform including at least one processor and memory: preparing sequence data for a plurality of overlapping RNA segments derived from a target sequence; inputting the sequence data for the plurality of overlapping RNA segments into a machine learning model trained to predict a probability of an interaction between a RNA sequence and a RNA binding protein occurring in a RNA sequence; outputting from the machine learning model one or more segments in the sequence data for the plurality of overlapping RNA segments falling above a probability threshold indicative of a region of interaction between a RNA sequence and a RNA binding protein; and predicting one or more binding sites between a RNA sequence and a RNA binding protein in the sequence data for the plurality of overlapping RNA segments derived from the target sequence based on the output from the model.

A method for the precise cellular destruction of an oncogenic non-coding RNA with a RNA-binding small molecule conjugated with bleomycin A5 is described. The method affords reversal of phenotype. Bleomycin A5 was coupled to an RNA-binding molecule that selectively binds the microRNA-96 hairpin precursor (pri-miR-96). By coupling of bleomycin A5's free amine to the RNA-binding molecule, its affinity for binding to pri-miR-96 is >100-fold stronger than to DNA. The conjugate compound selectively cleaves pri-miR-96 in triple negative breast cancer (TNBC) cells. Selective cleavage of pri-miR-96 enhances expression of FOXO1 protein, a pro-apoptotic transcription factor that miR-96 silences, and triggers apoptosis in TNBC cells. No effects were observed in healthy breast epithelial cells. This method provides programmable control for targeting RNA through the selection of an RNA-binding molecule / bleomycin A5 conjugate and provides a facile method of mapping the cellular binding sites of an RNA-binding molecule.

The invention discloses an RNA (Ribonucleic Acid) target region enrichment method based on a circular probe, and belongs to the technical field of biomolecule detection and gene sequencing. The method comprises the following steps: designing an annular probe containing an anchoring sequence, a UMI sequence and a universal primer sequence (at least one anchoring sequence 5'end is phosphorylated and modified); the method comprises the following steps: hybridizing a probe with target RNA (Ribonucleic Acid), enriching a hybridization compound through oligo d (T) magnetic beads, cyclizing the probe through DNA ligase, and carrying out PCR (Polymerase Chain Reaction) amplification to obtain an enriched product. Reverse transcription and extension steps are not needed, a solid-phase substrate is not needed, the experimental process is simplified, and the operation time is shortened; through combination of specific probe design and magnetic bead enrichment, high-selectivity enrichment of target RNA is realized, the method is especially suitable for differential expression analysis of samples with low expression quantity, and the template recovery rate and the effective data proportion are effectively improved.

The present invention relates to a dual-target double-stranded RNA for treating hepatitis B, and a pharmaceutical composition. The dual-target double-stranded RNA comprises a first double-stranded RNA and a second double-stranded RNA, wherein one of the first double-stranded RNA and the second double-stranded RNA targets the hepatitis B virus (HBV) life cycle, and the other targets a host immune target PD-L1. The double-stranded RNA can simultaneously target the dual targets of HBV and host immune PD-L1, which can inhibit HBV replication while activating human immunity, and is therefore expected to bring about a clinical functional cure.

The present disclosure relates to the technical field of targeted delivery lipids, in particular to a cationic polymer, a lipid composition comprising the same and applications thereof. The cationic polymer provided by the present disclosure has a structure shown in formula (I), and the lipid nanoparticles prepared therefrom can be used for RNA targeted delivery, and can significantly enhance the targeting effect of mRNA drugs on liver or spleen.

The embodiments disclosed herein utilized RNA targeting effectors to provide a robust CRISPR-based diagnostic with attomolar sensitivity. Embodiments disclosed herein can detect broth DNA and RNA with comparable levels of sensitivity and can differentiate targets from non-targets based on single base pair differences. Moreover, the embodiments disclosed herein can be prepared in freeze-dried format for convenient distribution and point-of-care (POC) applications. Such embodiments are useful in multiple scenarios in human health including, for example, viral detection, bacterial strain typing, sensitive genotyping, and detection of disease-associated cell free DNA.

The invention relates to the technical field of biomedical detection, and discloses a system for accurately detecting background signal subtraction of free RNA (Ribonucleic Acid) for early diagnosis of lung cancer. Comprising a sample collection module used for obtaining whole blood of a detected sample; a base signal determination module for determining a base signal level based on the whole blood; the measured value recording module is used for recording the measured value of the differentiated cancer tissue specific RNA transcript in the plasma; the machine learning subtraction module is used for carrying out signal subtraction processing on the basic signal level and the measured value through a random forest machine learning method; and the artificial selection module is used for carrying out qualitative selection on the cancerous genome region after the signal deduction processing, and realizing background signal deduction of free RNA in the non-small cell lung cancer pathological sample and accurate verification of the cancerous genome region in combination with a selection result corresponding to the qualitative selection so as to assist in early diagnosis of lung cancer. Background signals are efficiently reduced, and tissue-specific RNA targets are accurately screened.

Compositions, kits, and methods are provided for validating patient-specific oligonuclotide assays using spike-in controls. The compositions comprise multiple sets of spike-in oligos, each set including a unique reference sequence and near-neighbor sequences with at least one substitution, insertion, or deletion. Near-neighbor concentrations are less than the reference and collectively span at least four orders of magnitude (e.g., 1:10 to 1:10,000); all sets have the same number of near-neighbors and concentration ratios. Spike-in sequences are unrelated to human sequences and are complementary to synthesis-control oligos at known concentrations. Kits further include synthesis-control oligos and patient-specific oligos for human DNA or RNA targets. Methods involve spiking a sample, co-synthesizing control and patient-specific oligos, assaying by PCR or sequencing, and validating limit of detection and dynamic range by comparing observed counts to known ratios. Applications include ctDNA and cfRNA testing.

The invention belongs to the technical field of molecular biological detection, and particularly relates to application of lysine in LAMP (loop-mediated isothermal amplification) or preparation of LAMP products. In a conventional LAMP reaction system containing a template, a primer, a buffer solution and an enzyme, lysine is innovatively introduced as a reaction synergist, it is found that non-specific amplification can be effectively inhibited, the false positive rate is remarkably reduced, meanwhile, the detection sensitivity is improved by 27.5%, and the amplification efficiency is improved by 30.4%. The method has good universality, can be suitable for detection of DNA and RNA targets at the same time, and provides a reliable technical scheme for rapid and accurate clinical diagnosis.

The application relates to a gene editing nanorobot and a preparation method and application thereof, the preparation method comprising the following steps: S1, assembling an effector protein of a CRISPR / Cas system and a guide RNA to form a complex, and crosslinking the complex to form an RNP nanocluster; S2, preparing a hybrid vesicle by using a liposome and a biologically derived vesicle; S3, loading the RNP nanocluster into the hybrid vesicle; and S4, coupling activated glucose oxidase to the surface of the hybrid vesicle to obtain the gene editing nanorobot. The gene editing nanorobot is prepared by using the preparation method. The application is applied to targeted delivery in tumor cell gene editing, RNA target regulation or gene expression regulation. The gene editing nanorobot can load a gene editing system of the effector protein of the CRISPR / Cas system, has environmental responsiveness and autonomous motion capability, and can effectively improve the delivery efficiency and application performance in gene editing.

The application provides a medicine for treating an immune checkpoint inhibitor-resistant tumor, comprising a polyunsaturated fatty acid, an ACLY inhibitor and an immune checkpoint inhibitor. The polyunsaturated fatty acid comprises one or more of omega-3 polyunsaturated fatty acids and omega-6 polyunsaturated fatty acids. The ACLY inhibitor is selected from one or more of the following: Bempedoic acid, SB 204990, NDI-091143, BMS-303141, small interfering RNA targeting the ACLY gene and short hairpin RNA targeting the ACLY gene. The medicine has good treatment effect on the immune checkpoint inhibitor-resistant tumor.

The present invention features RNA polynucleotide constructs comprising a sequence that targets Huntingtin mRNA, polynucleotide constructs comprising a sequence encoding such RNA constructs, and primary microRNA scaffolds. The sequences that comprise and / or encode targeted Huntingtin mRNA may be used, for example, to inhibit the expression of mutant HTT and / or to treat Huntington's disease.

This invention provides an optimized method for enhancing self-amplifying RNA expression and an enhanced self-amplifying RNA. Specifically, it provides an optimized method for enhancing self-amplifying RNA expression, which involves codon optimization. The optimized region is a specific region of the alphavirus non-structural protein sequence of the self-amplifying RNA, where the alphavirus non-structural protein is nsP1234. It also provides a method for preparing the enhanced self-amplifying RNA, an enhanced self-amplifying RNA, and a plasmid. This application improves the expression efficiency of the self-amplifying RNA target gene by designing and constructing codon sequence optimization for certain regions of these non-structural proteins.

The present disclosure provides compounds of the formulae herein (e.g., Formulae (I) or (II)), and pharmaceutically acceptable salts thereof, which are degrader compounds of Quiescin Sulfhydryl Oxidase 1 (QSOX1) mRNA. The present disclosure also provides pharmaceutical compositions and kits comprising the compounds, or pharmaceutically acceptable salts thereof, and methods of treating or preventing diseases. Related compounds and methods useful in probing RNA targets and studying molecular recognition patterns between RNA and ligands are described.

RNA interference-based nucleic acids encoding double homeobox 4 (DUX4)-encoding guide RNAs (gRNA), or gRNAs that specifically hybridize to a target nucleic acid encoding DUX4 and methods for inhibiting the expression of DUX4 using the gRNAs and Cas13 are provided. The methods have application in the treatment of muscular dystrophies including, but not limited to, facioscapulohumeral muscular dystrophy (FSHD), and cancer, and other disorders associated with elevated DUX4 expression.

Short multi-repeat RNA targeting constructs for manipulating RNA targets and obtaining variable levels of gene silencing, and methods of using the same to silence RNA targets in mammals, insects, plants, and fungus. The constructs comprise two or more distinct guide nucleotide sequences (in the absence of CRISPR nuclease) that are complementary to one or more RNA targets, wherein each guide nucleotide sequence consists of a single-stranded antisense nucleotide fragment of 100 nt or less.

The application discloses a compound drug-loaded exosome for overcoming cancer TRAIL drug resistance and a preparation method thereof, relates to the technical field of compound nano-drug preparation, and comprises an engineered exosome and an interfering RNA targeting a natriuretic peptide receptor A gene, wherein the engineered exosome is derived from a cell capable of expressing a tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and carries the TRAIL protein; the interfering RNA is loaded in the engineered exosome; and the engineered exosome and the interfering RNA synergistically act to silence the NPRA gene through the interfering RNA to overcome the drug resistance of cancer cells to TRAIL. The application can silence the NPRA gene and remodel the apoptosis sensitivity of tumor cells through multiple channels, thereby efficiently overcoming the TRAIL drug resistance.

Provided is an interfering RNA targeting Janus kinase 1 (JAK1). The interfering RNA can reduce the expression of JAK1 and further inhibit the activation of a JAK / STAT signaling pathway, thereby achieving the purpose of treating a JAK / STAT signaling pathway dysregulation-associated disease. Further provided is a lipid nanoparticle drug containing the interfering RNA for use in treating a JAK / STAT signaling pathway dysregulation-associated disease. Further provided is an antibody-nucleic acid drug conjugate containing the interfering RNA for use in treating a JAK / STAT signaling pathway dysregulation-associated disease.

Disclosed herein are Advanced RNA Targeting (ARNATAR) oligomeric compounds, thoughtfully designed compounds for inhibiting gene expression through the RISC pathway. Such compounds are useful in methods for reducing expression of certain genes, many of which are associated with a variety of diseases and disorders.

Multiplexed fluorescent imaging methods are essential for resolving cellular transcriptional state with high resolution spatial information, but multiplexity is mostly limited to low numbers because of spectral overlap between the fluorophores that can be used. Although sequential fluidic exchange of DNA imagers expands its multiplexity, it requires time-consuming workflows and complex instrumentation. To eliminate such problems, here the toehold-FISH method as well as pre-programmed DNA probes is introduced, which is a novel imaging method that uses rapid and orthogonal DNA strand displacement reactions to enable highly multiplexed RNA imaging without buffer exchange steps and necessary accessories. In toehold-FISH, signal switching from one RNA target to the next is achieved by strand displacement reactions with sequentially added non- fluorescent DNA displacer strands, which take less than 30 seconds to complete signal switching in fixed cells. Because of vast sequence design space of DNA probes, unlimited multiplexity can be achieved.

The disclosure provides programmable methylation “writers” and demethylation “erasers” for editing the methylation state of RNA targets, e.g., an RNA transcriptome. In particular, the disclosure provides RNA methylation editor polynucleotide constructs and vectors comprising (i) an RNA programmable RNA binding domain (RNApRNAbd); and (ii) an effector domain, wherein the effector domain is capable of adding or removing a methyl group in an RNA. The disclosed RNA methylation editor constructs are capable of achieving limited off-target modifications in RNA molecules. Further, the disclosure provides methods for making and using the programmable methylation editors to modifying the methylation state of RNA. The disclosure further provides complexes comprising a methylation writer protein and a guide RNA molecule and complexes comprising a demethylation eraser protein and a guide RNA molecule. The disclosure further provides pharmaceutical compositions and cells comprising the disclosed fusion proteins and complexes.

The present invention provides an interfering RNA targeting TOP1 gene. The interfering RNA can reduce the expression of TOP1, thereby treating a disease related to TOP1 expression. The present invention further provides a lipid nanoparticle drug comprising the interfering RNA for treating a disease related to TOP1 expression. The present invention further provides an antibody-nucleic acid conjugate drug comprising the interfering RNA for treating a disease related to TOP1 expression.

The present disclosure provides a technique for suppressing the proliferation of cells. A double-stranded RNA disclosed herein comprises a first strand and a second strand. The first strand comprises a main sequence comprising 19-23 bases. The second strand comprises a complementary sequence that complementarily binds to the main sequence. The main sequence is a part of the nucleotide sequence encoding prosaposin and comprises the nucleotide sequence represented by SEQ ID NO: 1.

The invention discloses a triphenylphosphonyl imidazole compound, a compound and application, the triphenylphosphonyl imidazole compound provided by the invention is used as an RNA 2 '-hydroxyl reversible protective agent, the stability and controllable release of an RNA drug are improved, and targeted mitochondrial delivery of siRNA under the condition of not damaging cells is successfully realized; in addition, effective silencing of specific mitochondrial genes can be achieved, the aim of inhibiting tumors is achieved by weakening the normal function of mitochondria, and experience and possibility are provided for achieving mitochondrial disease treatment through RNA targeted delivery.

The present invention relates to a method of quantifying the amount of at least one nucleic acid target, the method comprising: a) providing a prescribed number of cells wherein the prescribed number of cells is at least one cell; and b) lysing the at least one cell, thereby releasing RNA and DNA; and c) performing a reverse transcription reaction on the released RNA thereby producing complementary DNA (cDNA) and further performing a digital polymerase chain reaction (dPCR) on at least one reverse transcribed RNA target within the cDNA and / or performing a digital polymerase chain reaction (dPCR) on at least one DNA target within the released DNA wherein the dPCR is performed in a plate, and d) quantifying the amount of the at least one nucleic acid target.

The invention provides an RNA (Ribonucleic Acid) and small molecule compound co-delivery system as well as a preparation method and application thereof, the co-delivery system takes a metal organic framework as a carrier, and the carrier is entrapped with RNA targeting KHSRP and a small molecule compound. The co-delivery system disclosed by the invention can target KHSRP to deliver RNA in vivo, so that the KHSRP gene is silenced, and meanwhile, the release of small molecule compounds is promoted to inhibit the expression of the KHSRP. Compared with single medication of the small molecule compound, the co-delivery system of the RNA and the small molecule compound provided by the invention has a better cancer treatment effect, and the co-delivery system provided by the invention has good biological safety.

The present disclosure provides a method for multiplexed RNA quantification, comprising: initiating an enzymatic reaction by mixing a reaction mixture, the reaction mixture comprising a CRISPR effector protein, a target-specific crRNA, a fluorescent reporter molecule, T7 RNA polymerase, an input sample, and a reaction buffer; capturing a plurality of fluorescence measurements, each fluorescence measurement captured at a different point in time; and determining a plurality of relative target concentrations by fitting the plurality of fluorescence measurements to a mathematical model of the enzymatic reaction. The method enables highly multiplexed quantification of RNA targets using CRISPR-based detection.