14 results about "Precursor mRNA" patented technology

A method and compound for regulating SCN1A gene mRNA and protein expression. Provided is a use of a guide agRNA in preparation of a drug for altering expression of a target protein in a cell of a subject. The cell has a precursor mRNA encoding the target protein, wherein the precursor mRNA comprises an intron, an exon flanking a 5' splice site of the intron, and an exon flanking a 3' splice site or a pseudo 3' splice site of the intron; the guide agRNA is capable of binding to the precursor mRNA to form a structure capable of recruiting ADAR in the cell, thereby forming a complex containing an ADAR protein; and the target protein is a Nav1.1 protein. By regulating alternative splicing of a target gene pre-mRNA, the functional RNA of the target gene and the function or expression of the target protein are affected, thereby achieving the objective of disease treatment.

The present invention relates to an antisense oligonucleotide (oligomer) complementary to NAT8L (N-acetyltransferase 8-like) precursor mRNA, which is capable of inhibiting the expression of NAT8L in a cell that expresses NAT8L. Inhibition of the expression of NAT8L is beneficial to the treatment of Canadian disease (Canadian disease).

The present application provides a method of inducing precursor mRNA exon skipping in a host cell comprising introducing into the host cell a deaminase recruitment RNA (dRNA) or a construct comprising a nucleic acid encoding the dRNA wherein the dRNA is a circular RNA (circRNA) or forms a circular RNA in the host cell.

The invention provides antisense oligonucleotide for regulating and controlling IL1RL2 gene variable splicing as well as a preparation method and application of the antisense oligonucleotide. Specifically, the invention provides an antisense oligonucleotide which interferes with variable splicing of an IL1RL2 gene, thereby inducing the generation of a truncated or concealed exon insertion type IL1RL2 splicing isomer transcript. The antisense oligonucleotide therapy provided by the invention can reduce the proportion of mRNA for coding full-length functional IL-36R and realize activation and blocking of an IL-36R signal channel by inducing splicing jump of an exon 4 or an exon 10 of an IL1RL2 gene precursor mRNA or splicing insertion of a hidden exon sequence of an intron 8. The compound can be used for treating autoimmune diseases, allergic diseases, neurodegenerative diseases or cancers related to abnormal activation of IL-36R.

The invention relates to the technical field of plant genetic engineering, in particular to a gene down-regulation method based on regulation of precursor mRNA (messenger Ribonucleic Acid) splicing efficiency, which comprises the following steps: firstly, identifying at least one intron 5'terminal splicing site containing a GT sequence in a target gene; aiming at the site, designing a guide RNA (Ribonucleic Acid) sequence capable of targeting the downstream fourth or fifth nucleotide, and verifying the cleavage activity of the guide RNA sequence; constructing a gene editing vector by using the guide RNA sequence which is verified to be effective and a Cas9 nuclease coding gene; introducing the vector into a plant cell, carrying out genetic transformation and regeneration to obtain a transformed plant, and screening out a mutant which is subjected to site-directed editing at a target site through DNA (Deoxyribose Nucleic Acid) sequencing; and finally, extracting RNA (Ribonucleic Acid) of the mutant, reversely transcribing into cDNA (Complementary Deoxyribonucleic Acid), and analyzing transcript change through PCR (Polymerase Chain Reaction) amplification and gel electrophoresis. According to the invention, stable, heritable and accurate knock-down of gene expression is realized, and a new tool is provided for essential gene function research and crop character improvement.

The present invention provides precursor mRNA splicing conversion or modulation oligonucleotides comprising a bicyclic scaffold moiety having improved features in the treatment of genetic diseases. The present invention provides antisense splice transition oligonucleotides having improved features that enhance clinical applicability for treating, ameliorating, preventing and / or delaying neuromuscular diseases, such as DMD.

Provided herein are methods for assessing splice transition ASO using a reporter to detect splice of a concealment sequence located in a reporter precursor mRNA.

Provided herein are pharmaceutical formulations, kits and methods of their use for treating a disease or condition by modulating the expression of NaV1.1 protein in a cell of a subject in need thereof wherein the ASO modulates splicing of a non-sense mediated mRNA decay-inducing exon from a precursor mRNA in the cell of the subject, thereby modulating the expression of the NaV1.1 protein in the subject.

Provided is a guide agRNA for regulating RNA splicing. Also provided is use of the guide agRNA in the preparation of a drug for changing the expression of a target protein by cells of a subject. The guide agRNA recruits the ADAR protein to the 3' splice site or pseudo-3' splice site to edit the base A of the 3' splice site or pseudo-3' splice site, so that an entire exon flanking the 3' splice site or pseudo-3' splice site of the intron is spliced from the precursor mRNA, thereby changing the level of the mRNA encoding the target protein and the expression of the target protein in the cells. That is, the selective splicing of the pre-mRNA of the target gene is regulated to affect the function or expression of the functional RNA and target protein of the target gene, achieving the purpose of treating diseases.

Disclosed are a multi-vector expression system encoding precursor mRNA molecules and precursor mRNA trans-splicing molecules (PTM), and a cultured eukaryotic recombinant host cell comprising the system. Furthermore, disclosed are a method for recombinantly expressing one or more target proteins in a cultured eukaryotic host cell line, and a method for screening a eukaryotic host cell recombinantly expressing a target protein in vitro, which employ the multi-vector expression system of the present application.

The present invention relates to a method of modulating selective splicing of a precursor mRNA encoding an advanced glycosylation end product receptor (RAGE) or a portion thereof using an antisense oligonucleotide (AON) to modify the expression and / or activity of RAGE isoforms. In one aspect, the invention provides a method for promoting the production of endogenous soluble RAGE and / or reducing the production of membrane-bound RAGE (mRAGE) in a subject, the method comprising: in a first administration, administering to the respiratory tract of the subject an antisense oligonucleotide (AON) that promotes the production of endogenous soluble RAGE and / or reduces the production of membrane-bound RAGE (mRAGE), in a second administration, AON that promotes the production of endogenous soluble RAGE and / or reduces the production of membrane-bound RAGE (mRAGE) is administered to the respiratory tract of the subject, where the second administration is at least about 7 days after the first administration, thereby promoting the production of endogenous soluble RAGE and / or reducing the production of membrane-bound RAGE (mRAGE) in the subject.

An HTT nucleic acid trans-splice molecule is described that includes a coding domain comprising one or more HTT exons, a splice site, and a binding domain that binds to a target intron of an HTT precursor mRNA. The HTT nucleic acid trans-splice molecules described herein may also be used in combination with, for example, an MSH3 binding domain aligned in series with an HTT binding domain, an MSH3 nucleic acid trans-splice molecule, an MSH3 splice modulator, an antisense oligonucleotide or antisense RNA for either of MSH3 or HTT, and an MSH3 or HTT microRNA (miRNA) and constructs encoding them. Also encompassed are compositions comprising the nucleic acid trans-splice molecules described herein, as well as compositions comprising a nucleic acid trans-splice molecule in combination with an additional therapeutic agent (e.g., an MSH3 nucleic acid trans-splice molecule, an MSH3 splice modulator, an antisense oligonucleotide or antisense RNA for any one of MSH3 or HTT). The nucleic acid trans-splicing molecules may be used alone or in combination with additional therapeutic agents in methods of treating Huntington's disease (HD). Also described herein are nucleic acid trans-splice molecules for use in the treatment of HD or in the preparation of medicaments for the treatment of HD, alone or in combination with additional therapeutic agents. Also encompassed herein are MSH3 nucleic acid trans-splice molecules, MSH3 splice modulators, and MSH3 miRNAs, as well as constructs encoding them, which can be used, alone or in combination and / or in combination with additional therapeutic agents, for the treatment of nucleotide repeat disorders (e.g., HD) or for the preparation of medicaments for the treatment of nucleotide repeat disorders (e.g., HD).

The present invention relates to a method for identifying a RAGE precursor mRNA splice that results in inclusion of exon 9b and / or exclusion of exon 10 in a subject that has received or is receiving an antisense oligonucleotide that modulates the RAGE precursor mRNA splice. In one aspect, the invention provides a method for determining an endogenous soluble advanced glycosylation end product receptor (RAGE) level in a lung of a subject, the method comprising: determining the presence of an endogenous soluble RAGE in a blood sample from the subject that has received or is receiving a treatment administered to a respiratory tract thereof, wherein the treatment increases endogenous soluble RAGE, and wherein the level of endogenous soluble RAGE in the blood sample is associated with the level of endogenous soluble RAGE in the lung of the subject.

The present application relates to the field of tumor immunotherapy, discloses a kind of ribozyme for targeted inhibition of PD-L1 gene expression and its preparation method and application, specifically relates to a kind of engineered Pistol ribozyme and its use in targeted inhibition of PD-L1 (CD274) gene expression.The ribozyme is RNA molecule connected by ribonucleotide monomer, contains the substrate recognition region of the conserved structural framework maintaining catalytic activity and PD-L1 transcript complement;Conserved skeleton covers P1, P2, P3 region and false node area, and contains catalytic related conserved base site, substrate recognition region can be designed as required, can recognize and cut the targeted site containing GU dinucleotide in PD-L1 transcript, reduce the PD-L1 expression of tumor cell in post-transcriptional level.The PD-L1 transcript includes mature mRNA, precursor mRNA, intron retention transcript and variable splicing transcript.Different from existing immune checkpoint blockade therapy, the present application can sustainably inhibit endogenous PD-L1 in tumor cell, relieve immune suppression, enhance anti-tumor immune response, and also provide the preparation method of the ribozyme and its pharmaceutical composition, and application prospect is good.