468 results about "Circular RNA" 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.

The present disclosure relates, generally, to methods for producing, purifying, and using circular RNA from a prokaryotic system.

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 relates to the technical field of biological medicines, discloses application of circPDK1 protection, and particularly relates to application of a reagent for specific detection of circPDK1 in preparation of products for detection of esophageal cancer or prognosis evaluation of esophageal cancer. According to the application of the protected circular RNA in preparation of the esophageal cancer detection product, the circular RNA is circPDK1, and the nucleotide sequence of the circular RNA is shown as SEQ ID NO: 1. Experiments prove that circPDK1 is highly expressed in esophageal cancer tissues, growth, proliferation and migration of esophageal cancer cells are promoted, occurrence of esophageal cancer is promoted, knock-down of the circular RNA can significantly inhibit growth, proliferation and migration of esophageal cancer tumors, and the average survival time of esophageal cancer patients with low circPDK1 expression is longer than that of esophageal cancer patients with high circPDK1 expression. And a new research direction is provided for esophageal cancer detection, treatment and prognosis.

According to the invention, a structural domain reaction substrate sequence consisting of Exon1 (E1), P1 and Exon2 (E2) sequences of ribozyme is mutated, and E1, P1 and E2 sequences are mutated under the condition of maintaining the structural stability, so that the Azoarcus group I intron ribozyme still has enzyme activity and can maintain the capability of forming circular RNA (Ribose Nucleic Acid). The invention discloses a flexible vector construction method for preparing circular RNA (Ribonucleic Acid) without limitation of a substrate sequence, which comprises the following steps: determining a target to-be-cyclized site sequence NNUNNNN, and segmenting the target to-be-cyclized site sequence NNUNNNN into E1: NNU and E2: NNNN; with E1 and E2 sequences as references, designing IGS sequences to respectively form complementary pairing with E1 and E2; and 5'and 3 'homologous arms, IRES, CDS and other elements are respectively added. The method provided by the invention can be used for preparing the circular RNA for any target sequence, has no residual sequence, and has relatively high cyclization efficiency. The FlexCirc cyclization system designed on the basis of Azoarcus group I intron ribozyme can form the circular RNA, the cyclization substrate sequence has the characteristic of flexible design, and the cyclization efficiency can realize a relatively high cyclization proportion.

The invention discloses a circular RNA drug sensitivity correlation identification method based on integrated multi-instance learning. The circular RNA drug sensitivity correlation identification method comprises the following steps: collecting experimental verification circular RNA and drug sensitivity correlation data; establishing a feature representation model based on a heterogeneous network and vertexes; embedding a heterogeneous graph node into the model, and extracting deep feature representation of the node; designing a meta-path instance embedding projector, and generating a plurality of meta-path instances; a circular RNA and drug sensitivity association predictor is constructed and completed; constructing an integrated heterogeneous graph network deep learning model; and outputting the meta-path instance of the circular RNA and drug pair and the attention coefficient, and carrying out interpretable analysis. According to the method, integrated learning and a deep learning model are combined, so that the reliability of the model is improved; according to the invention, interpretable analysis is carried out by utilizing the meta-path and the attention coefficient, the potential action mechanism of the circular RNA associated with the drug sensitivity can be explained, and the guidance of medical research is facilitated.

The invention relates to the technical field of gene engineering. The invention provides a functional sequence shRNA1 (short hairpin ribonucleic acid 1) for silencing a circular RNAh-hsacirc005838, and further provides a lentiviral vector of the functional sequence shRNA1 and a construction method of the lentiviral vector. The invention also provides a lentivirus packaging titer kit containing the lentiviral vector with the functional sequence shRNA1, and also provides an application of the lentiviral vector with the functional sequence shRNA1 or the lentiviral vector with the functional sequence shRNA1 in preparation of a kit for breast cancer diagnosis. According to the invention, an interference target sequence siRNA1 is obtained by aiming at the annular target gene RNA h-hsacirc005838, then the finally obtained functional sequence shRNA1 can directly and efficiently infect cells and silence the annular RNAh-hsacirc005838 sequence, and the transfection effect is stable.

The invention provides a non-small cell lung cancer auxiliary diagnosis composition and application and a kit thereof, and relates to the technical field of biological detection.The non-small cell lung cancer auxiliary diagnosis composition comprises a circular RNA ALG8 primer and a circular RNA CAMTA1 primer, circALG8 and circCAMTA1 can be used as markers of early non-small cell lung cancer liquid biopsy, and the non-small cell lung cancer auxiliary diagnosis composition can be applied to diagnosis of non-small cell lung cancer. According to the present invention, with the application of the circALG8 primer and the circCAMTA1 primer, the plasma circALG8 and circCAMTA1 combined diagnosis model can be successfully constructed, the NSCLC patient and the healthy control can be effectively distinguished, the area under the curve is up to 0.8987 when the circALG8 primer and the circCAMTA1 primer are combined to identify the efficiency of the early NSCLC, the identification result has extremely high accuracy, the diagnosis accuracy is significantly improved, the sensitivity reaches 91.78%, and the specificity reaches 75.53%.

The present disclosure relates, generally, to compositions and methods for producing, purifying, and using circular RNA.

The application discloses a kind of based on shared unit's circular RNA and the construction method of disease association prediction model, prediction system and prediction method, and the association prediction is realized by the circular RNA and the disease association prediction model constructed, comprising: based on known association dataset constructs circular RNA meta-path network, circular RNA similarity network, disease meta-path network and disease similarity network, the feature extraction of the aforementioned network respectively obtains circular RNA similarity feature, circular RNA meta-path feature, disease similarity feature and disease meta-path feature;Similarity feature and meta-path feature are simultaneously input into shared unit;The similarity feature output by shared unit is input into multilayer perception machine to carry out the association prediction of circular RNA and disease and update model parameter.Share unit is designed for model, and the similarity network and meta-path network of circular RNA and disease are constructed, and potential cross-view information is captured in the process of multi-view feature fusion, so as to improve the prediction performance of model.

Provided is a circular RNA encoding CARs and the use thereof to create immune cells that target specific diseases, e. g., lymphoma, multiple myeloma and leukemia and auntoimmune diseases, such as systemic lupus erythematousus, lupus nephritis and myasthenia gravis.

The invention discloses preparation and application of porcine reproductive and respiratory syndrome virus circular RNA (Ribonucleic Acid) and a vaccine. The circular RNA encodes and expresses GP5 protein optimized by the porcine reproductive and respiratory syndrome virus and M protein optimized by the porcine reproductive and respiratory syndrome virus. The optimized circular RNA molecule is prepared into a vaccine to successfully induce a high-level neutralizing antibody in a pig body, so that the proportion of CD4 + IFN-gamma + and CD8 + IFN-gamma + cells in PBMC cells is remarkably increased, the lymphocyte proliferation activity after specific stimulation of a virus antigen is remarkably improved, and the protection of the porcine reproductive and respiratory syndrome virus is effectively realized. The invention provides a basis for preparing the RNA vaccine for preventing and / or treating the porcine reproductive and respiratory syndrome virus.

The present invention relates to a plasmid vector for synthesizing a self-circularization RNA structure in an in vitro transcription (IVT) process and to a DNA fragment for preparing same. The present invention can be used in a method for efficiently and economically producing circular RNA in large quantities under an STS system.

The present invention provides nucleic acids and methods for making circular RNAs (circRNAs), compositions comprising circular RNAs, and methods of use thereof. The present invention uses optimized self-splicing T4 bacteriophage td gene (T4td) intron sequences to produce circular RNAs. The optimized T4td intron sequences described herein mediate efficient circularization of a linear RNA sequence.

Provided is an application of a circular RNA in the preparation of a cerebral stroke diagnosis product, belonging to the field of circular RNA medical treatments. Provided is a kit, comprising a reagent and / or test paper and / or gene chip for detecting a circular RNA-circ-Magi1. The nucleotide sequence of the circular RNA-circ-Magi1 is as shown in SEQ ID NO: 1 or SEQ ID NO: 4. Further provided is the application of a detection system for the diagnosis, assisted diagnosis or prognosis evaluation of cerebral stroke, and a detection reagent of the circular RNA-circ-Magi1 in the preparation of a kit, test paper, chip or high-throughput sequencing platform for the diagnosis, assisted diagnosis or prognosis evaluation of cerebral stroke.

The invention discloses an NDRV [sigma] C circular RNA vaccine and application thereof, and belongs to the technical field of vaccines.Duck hepatitis A virus type 1 (DHAV-1) UTR and T4 bacteriophage I type intron self-splicing cyclization systems are adopted to construct circular RNA (CirRNA-[sigma] C) for expressing NDRV [sigma] C protein, and a vaccine preparation is prepared through a chitosan-polyethyleneimine (CS-PEI) nano delivery system. The feasibility of a circular RNA vaccine system based on DHAV-1UTR in poultry vaccines is confirmed for the first time, the established nano delivery technology and circular RNA vaccine platform have the characteristics of high stability, good safety, strong immunogenicity and the like, and an important technical path is provided for development of novel vaccines of NDRV and other viral epidemic diseases.

The invention belongs to the field of biological medicine, and provides circular RNA for treating multiple endocrine tumor type I and application of the circular RNA. According to the invention, after different optimization and design are carried out on the circular RNA for coding Menin, the circular RNA with relatively good expression level and long half-life period is finally obtained, and the anti-tumor effect is mainly achieved by supplementing cell-deficient Menin. Compared with the prior art, the circular RNA for expressing the Menin protein provided by the invention is more stable in intracellular expression and longer in half-life period. In an immortalized parathyroid gland cell model, the Menin protein can be expressed by transfecting the circular RNA for 6 hours, and the circular RNA has good treatment potential for multiple endocrine tumor type I.

The invention provides a circular RNA circ0004801 and an application of the circular RNA circ0004801 in treatment of an Alzheimer's disease. The nucleotide sequence of the circular RNA circ0004801 is as shown in SEQ ID NO: 1 (Sequence Identity Number 1). The expression of the circular RNA circ0004801 in the hippocampal tissue of the AD mouse is obviously up-regulated, and the circular RNA circ0004801 is used as a'sponge 'of miR-7688-5p and plays a role by adjusting the TTBK1 expression and tau phosphorylation level. By knocking down the circular RNA circ0004801, the spatial learning and memory of a 3 * Tg mouse can be obviously improved, and the tau protein phosphorylation level of a hippocampus region and the NFTs density of a hippocampus DG region can be obviously reduced. Therefore, the circular RNA circ0004801 and the miR-7688-5p can be used as new targets for treating the AD (Alzheimer's disease). According to the invention, it is found for the first time that circular RNA circ0004801 regulates TTBK1 through a ceRNA mechanism, so that excessive phosphorylation of tau is driven, and a new molecular target is provided for AD early intervention treatment based on circRNA and miRNA.

An iRGD-LAMP2B-EGFP fusion protein mediated exosome surface engineering strategy is adopted, through specific recognition of iRGD peptide and integrin alpha v beta 3, corneal neovascularization core lesion cells are actively targeted, the limitation of off-target toxicity of a traditional delivery system is broken through, and a'accurate focus recognition-efficient homing 'targeted delivery normal form is established. Meanwhile, the screened circular RNA with anti-inflammatory and anti-angiogenesis dual activities is used as a core effector molecule, and in combination with an in-situ loading technology of the circular RNA molecule in an exosome parent cell, stable entrapment and targeted release of a nucleic acid drug in an exosome cavity are realized, and the problems that the nucleic acid drug is easy to degrade and poor in targeting property are solved; and dual guarantee of function specificity and delivery stability is formed. And a synergistic treatment system of a targeting exosome carrier and bifunctional circular RNA is further constructed, active molecules are accurately delivered to focus cells, and an inflammation microenvironment and an angiogenesis pathway are synchronously regulated and controlled.

The invention provides an application of human source circular RNA hsacirc0083796 in preparation of a diagnostic reagent or a medicine for diagnosing and / or treating aortic dissection. The invention also provides a kit for diagnosing the aortic dissection. The invention also provides a pharmaceutical composition for treating aortic dissection. According to the application of the human source circular RNA in preparation of heart disease related products, the related heart disease related circular RNA (circled-Frizzled class receptor 3, hsacirc0083796) is one of circular RNAs with the highest expression quantity in the blood of aortic dissection patients and has high conservative property, the function of the circular RNA is closely related to heart diseases, and the circular RNA has a good application prospect in preparation of heart disease related products. The method has great significance in diagnosis and treatment of heart diseases. Meanwhile, due to the stable and specific properties of the circular RNA, compared with other types of markers, the circular RNA has larger abundance in body fluid of a patient and more obvious change, so that the circular RNA has the potential of becoming a novel diagnostic marker.

The present invention provides nucleic acids and methods for making circular RNAs (circRNAs), and circular RNAs, compositions and methods of use thereof. The present invention uses selected self-splicing intron sequences (e.g., intronic sequences derived from self-splicing Group I or Group II introns) to produce circular RNAs. These self-splicing intron sequences described herein mediate efficient circularization of a linear RNA sequence.

Provided are modified varicella-zoster virus (VZV) gE polypeptide, a circular RNA encoding the modified VZV gE polypeptide, a linear RNA encoding the modified VZV gE polypeptide and the use thereof for inducing an antigen specific immune response in a subject, or preventing or treating VZV infection.

The invention relates to a modified RNA with a synthetic cap structure and a modified coding region encoding for DNAse1 and / or DNAse1L3. The invention further relates to a saRNA and / or a circular RNA, and to a vector encoding the modified RNA. The invention also relates to a pharmaceutical composition for the use of treating a disease associated with the formation of extracellular DNA, including extracellular traps released from leukocytes, such as NETs.

Provided is a medicament for treating a disease related to motor neuron injury. The medicament comprises: a circular RNA having a circBank ID of hsa_circPTPRN2_018, and a proper diagnosis module and a drug carrier. Also provided is use of a circular RNA in preparing a medicament for diagnosing and treating a disease related to motor neuron injury.

The invention discloses a biological interpretability circular RNA automatic identification method, and belongs to the technical field of bioinformatics and computers. According to the method, sequence data is obtained from a database and preprocessed, reverse complement matching and ALU repeated element features are extracted, after the features are screened through an MRMD2.0 algorithm, a depth model combining a convolutional neural network and a bidirectional long-short-term memory network is constructed for classification training, feature contribution is analyzed through an SHAP method, and finally the model is applied to multiple scenes. According to the method, circRNA cyclization key features can be accurately captured, high-order feature representation is automatically learned to improve the classification accuracy, meanwhile, a feature biological mechanism is disclosed, multi-task migration such as circRNA and PCG distinguishing and stem cell expression prediction is achieved, and the defects of an existing algorithm in the aspects of feature representation and interpretability are overcome.

The invention relates to the technical field of biological medicines, in particular to application of hsacirc0008126 in prevention and treatment of senile osteoporosis. The invention provides the circular RNA hsacirc0008126 which can be used for regulating and controlling the mesenchymal stem cell osteogenesis and adipogenic differentiation, the mechanism of the circular RNA hsacirc0008126 on the mesenchymal stem cell osteogenesis and adipogenic differentiation is different from that of the prior art, the medicine taking the circular RNA hsacirc0008126 as the target spot can be used for treating and / or preventing osteoporosis, and the circular RNA hsacirc0008126 has important application value.

The invention provides an EVB-IRES-based annular RNA for coding a GLP-1 similar polypeptide and application of the annular RNA, and belongs to the technical field of molecular biology. The invention provides a circGLP1 recombinant plasmid and / or a circGLP1-FcBO recombinant plasmid based on EVB-IRES (Enterovirus Virus B-IRES). The circGLP1 recombinant plasmid comprises nucleotide sequences of Td-3, EVB-3, GLP1, 6xPolyAC, EVB-5 and Td-5, and the circGLP1 recombinant plasmid and the circGLP1-FcBO recombinant plasmid comprise nucleotide sequences of the Td-3, the EVB-3, the GLP1, the 6xPolyAC, the EVB-5 and the Td-5. The circGLP1-FcBO recombinant plasmid contains nucleotide sequences of Td-3, EVB-3, GLP1-FcBO, FcBO-6xPolyAC, EVB-5 and Td-5, and is characterized in that the nucleotide sequences of the circGLP1-FcBO recombinant plasmid are shown in the description. After the circular RNA-LNP is injected, the blood sugar of the mouse is continuously lower than the initial blood sugar within one week, which proves that the circular RNA-LNP can maintain the efficacy in vivo for at least one week.