110 results about "Mitochondrial RNA editing" patented technology

The present invention relates to antisense oligonucleotides (AONs) that can mediate RNA editing by binding to a target RNA nucleic acid molecule, preferably an RNA transcript molecule, in a cell and recruiting an endogenous deaminating enzyme in the cell to deaminate a target adenosine in the target RNA molecule to an inosine. The target RNA molecule is a transcript molecule form the SLC10A1 gene that encodes the Na+ / Taurocholate Co-transporting Polypeptide (NTCP), and the target adenosine is the adenosine in the GAC codon coding for aspartic acid (D) at position 24 of the NTCP protein. The deamination of the adenosine changes the amino acid to a glycine (G). The RNA editing of the adenosine will result in a loss-of-function of the NTCP protein, which will result in lowered uptake of bile acids from the portal circulation into the liver, thereby lowering the risk of suffering from disorders related to bile accumulation in the liver.

The invention relates to compositions and methods for RNA editing. In particular, ribozymes can be utilized to enhance RNA trans-splicing.

The invention discloses a chloroplast RNA edited gene OsPPR7 for temperature-sensitive regulation and control of rice and application of the gene OsPPR7, and belongs to the technical field of gene engineering. The CDS sequence of the OsPPR7 gene is as shown in SEQ ID NO. 1. The OsPPR7 is an RNA (Ribonucleic Acid) editing factor which has a bidirectional regulation and control function and is sensitive to temperature. Editing of multiple sites on the rpoB gene is negatively regulated and controlled, and meanwhile RNA editing of multiple genes such as ndhB and ndhD which are crucial to the chloroplast function is positively regulated and controlled under high-temperature stress. Under the stress of high temperature of 35 DEG C, the loss of functions can lead to obvious reduction of RNA editing efficiency of a plurality of ndh genes, and serious yellowing of seedlings is caused. The key function of the rice OsPPR7 gene in regulation and control of rice growth and development and high-temperature response is clarified for the first time, the importance of the OsPPR7 gene in maintenance of chloroplast functions under high-temperature stress is clarified, and a new gene resource and a technical path are provided for cultivation of new varieties of high-temperature-resistant rice.

The invention relates to compositions and methods for RNA editing. In particular, ribozymes can be utilized to enhance RNA trans-splicing.

The invention relates to chemically modified oligonucleotides comprising a sequence with a length of 23 to 80 nucleotides, capable of binding to a target sequence in a target RNA, comprising a central base triplet (CBT) of 3 nucleotides (5′—N−1eN0fN+1g-3′) with the central nucleotide (N0) directly opposite to the target adenosine in the target RNA, wherein the core oligonucleotide comprises the following sequence: 5′—N−5aN−4b N−3cN−2dN−1eN0fN+1gN+2h N+3 iN+4j-3′ comprising different 2′ sugar and linkage modifications. The present disclosure also provides oligonucleotides and compositions thereof for use in use in the treatment or prevention of a genetic disorder, condition, or disease. Also provided are methods for editing a target adenosine or deaminating at least one specific adenosine in a target nucleic acid.

The present disclosure relates generally to (CRISPR) RNA (crRNA) for the precision silencing of transcripts. In some embodiments, the crRNA are enriched for guanosine (G) nucleotides at key spacer positions, which is useful in enhancing the silencing efficacy of otherwise inefficient crRNA, thereby expanding the targeting spectrum of Cas13 endonucleases, e.g., Cas13b and Cas13d. In other embodiments, the crRNA comprise a spacer sequence having at least one nucleotide mismatch relative to the target RNA sequence, wherein the target RNA sequence is a wild-type transcript and / or a variant transcript (e.g., a transcript comprising a single nucleotide variant (SNV)). The present disclosure also provides RNA editing systems comprising the crRNA described herein in complex a Cas13 effector protein and a target RNA sequence, methods for the selective targeting of transcripts encoding proteins that are difficult to target, or are not amenable to pharmacological targeting, e.g., oncogenic fusion transcripts or oncogenic transcripts comprising single nucleotide variant(s), and methods for the design and selection of potent crRNA.

The present invention provides novel RNA base editing compositions, systems, methods and uses. Guide RNAs for site-specific RNA editing of RNA encoding transcriptional coactivators YAP1 or TAZ are provided, and compositions and systems comprising the same with a programmable RNA binding protein (e.g. a Cas protein) and / or a base editor. Methods for RNA editing of YAP1 or TAZ are also provided. RNA editing of YAP1 or TAZ is used for targeting phosphorylation sites, and activating transcription of proteins in regenerative therapy for treating cardiac disease.

The present invention relates to a method for the differential diagnosis of bipolar versus unipolar disorder in a human patient during a depressive phase from a biological sample of the patient, comprising determining the relative proportions of RNA editing variants of at least the A-to-I-edited RNA ZNF267 gene. The present invention also relates to a method for monitoring the treatment of a depressed patient exhibiting bipolar or unipolar disorder. Finally, the present invention provides a kit for the differential diagnosis of bipolar versus unipolar disorder in a patient during a depressive phase.

The invention relates to the field of diseases caused by alcohol intolerance, for example, diseases caused by ALDH2 * 2 mutation in the human ALDH2 gene. The present invention relates to oligonucleotides and their use in RNA editing methods for targeting a target adenosine in an endogenous human ALDH2 transcript in a cell, for example, Ggt in a mutant ALDH2 gene transcription molecule encoding a mutant p.E504K ALDH2 protein; a mutation, especially in the liver.

The application discloses a fusion protein, which comprises an antibody binding domain and an RNA editing domain, wherein the antibody binding domain is a pAG domain, which comprises the functional domains of Protein A and Protein G, and the RNA editing domain comprises a rat APOBEC1 enzyme deamination domain and / or a human ADAR2 enzyme deamination domain. The fusion protein can be used to simultaneously identify RBP targets and provide transcriptome information in the same sample, can characterize the RNA-protein interaction spectrum, has high reliability and sensitivity, is suitable for studying the RBP functions in tissue sections and single cells, and has wide application prospects in the functional mechanism research of RBP in the development and disease processes.

The present disclosure provides novel adenine base editors that retain ability to edit DNA efficiently but show greatly reduced off-target effects, such as reduced RNA editing activity, as well as lower off-target DNA editing activity and reduced indel by product formation. Also provided are base editing methods comprising contacting a nucleic acid molecule with an adenine base editor and a guide RNA that has complementarity to a target sequence. Further provided are complexes comprising a guide RNA bound to a base editor provided herein; and kits and pharmaceutical compositions for the administration of adenine base editor variants to a host cell.

A sequence for forming an editing substrate together with a target RNA editing site. The sequence and the upstream and downstream portions of the target RNA editing site form a specific double-chain secondary structure, so that efficient editing of the target RNA editing site is realized.

The invention relates to editing oligonucleotides (EONs) that carry stereospecific phosphorothioate internucleotide linkage modifications at specified positions and that do not carry such modifications on positions that would lower RNA editing efficiency. The selection of positions that should or should not carry a phosphorothioate Rp and / or Sp configuration modification is based on computational modelling that revealed incompatibilities of the stereospecific linkages with the intermolecular oxygen-mediated hydrogen bond network.

This disclosure provides methods for treating neurodegenerative diseases and restoring neuronal synaptic function by administering adenosine-to-inosine editing modifiers.

Disclosed herein are SnRNA systems containing RNA-binding sequences for RNA editing.

The invention discloses a corn ZmMORF3 gene, an excellent haplotype of the corn ZmMORF3 gene and application of the corn ZmMORF3 gene in grain development regulation and molecular breeding. A key gene ZmMORF3 which affects mitochondrial gene RNA editing is cloned by using a grain mutant m497 found in a corn field breeding line selection process, and the gene encodes MORF protein and regulates assembly and activity of a mitochondrial compound I, so that corn grain development is affected; the excellent allelic variation genotype of the ZmMORF3 gene in the aspect of the row grain number is further excavated, and the row grain number can be increased by utilizing the ZmMORF3 gene, so that the yield is increased. In addition, distribution and utilization potentials of different haplotypes in a selfing line are researched, and technical support and excellent germplasm resources are provided for utilization of the gene.

Provided is an RNA editing system activating a Wnt signaling pathway, relating to the field of gene editing. Provided is an RNA editing element, comprising an Axin1-targeting RNA fragment and an Axin2-targeting RNA fragment. A gRNA that targets both Axin1 and Axin2 is constructed, which, compared with gRNAs targeting Axin1 or Axin2 alone, can significantly up-regulate Wnt activity. An AAV6 vector is screened from three AAV vectors of different serotypes, and exhibits relatively high expression intensity and efficiency and high infection efficiency with respect to airway epithelial cells and alveolar epithelial cells while exhibiting very low infection efficiency with respect to immune cells and endothelial cells. The AAV vector is assembled with a Cre-LoxP recombinase system to together infect a host cell, thereby facilitating the measurement of Cas13d knockdown efficiency by means of fluorescent labeling.

The present invention relates to methods and compositions for disrupting interaction of an NRF2 protein and a KEAP1 protein. The methods include contacting at least one polynucleotide selected from the group consisting of a polynucleotide encoding the NRF2 protein and a polynucleotide encoding the KEAP1 protein with a guide oligonucleotide that effects one or more (e.g., at least two) adenosine deaminase acting on RNA (ADAR)-mediated adenosine to inosine alterations in said at least one polynucleotide, wherein the adenosine to inosine alterations generate a mutant amino acid, thereby disrupting interaction of the NRF2 protein and the KEAP1 protein. The invention also relates to methods of treating a KEAP1-NRF2 pathway related disease in a subject in need thereof, the method comprising contacting, within the subject, at least one polynucleotide selected from the group consisting of a polynucleotide encoding an NRF2 protein and a polynucleotide encoding a KEAP1 protein with a guide oligonucleotide that effects an adenosine deaminase acting on RNA (ADAR)-mediated adenosine to inosine alteration in said at least one polynucleotide, wherein the adenosine to inosine alteration generates a mutant amino acid, thereby disrupting interaction of the NRF2 protein and the KEAP1 protein and treating the disease in the subject; and compositions thereof.

The invention relates to chemically modified oligonucleotides for use in site-directed A-to-I editing of a target RNA inside a cell with endogenous adenosine deaminase acting on RNA (ADAR), the oligonucleotide comprising a sequence capable of binding to a target sequence in a target RNA and a central base triplet (CBT) of 3 nucleotides (N−1N0N+1), wherein N0 is the central nucleotide directly opposite to a target adenosine in the target RNA that is to be edited, wherein the oligonucleotide comprises at least one internucleoside linkage that is a methanesulfonyl (mesyl) linkage.

Provided herein are RNA editing oligonucleotides capable of effecting ADAR-mediated deamination of a target adenosine comprised in a target RNA, wherein the oligonucleotide comprises a sequence that is capable of hybridizing with a region in the target RNA comprising said target adenosine, and wherein the oligonucleotide comprises at least one conformationally restricted nucleotide (CRN) positioned at the 5' and / or at the 3' terminus of the oligonucleotide and / or internally. In particular, the target adenosine may be part of a therapeutic target codon in the MECP2 protein-coding RNA. Provided herein are RNA editing oligonucleotides capable of effecting ADAR-mediated deamination of a target adenosine in a target RNA molecule encoding a target protein, wherein the oligonucleotide comprises a sequence that is capable of hybridizing with a region in the target RNA molecule comprising said target adenosine, and wherein the target adenosine is part of a codon encoding a posttranslational modification site in the target protein. In particular, the target adenosine may be part of a ubiquitination site in the frataxin (FXN) protein. Provided herein are RNA editing oligonucleotides capable of effecting ADAR-mediated deamination of a target adenosine in a target RNA molecule encoding a target protein, wherein the oligonucleotide comprises a sequence that is capable of hybridizing with a region in the target RNA molecule comprising said target adenosine, and wherein the target adenosine is part of a start codon in the 5' untranslated region of the target RNA molecule. In particular, the target adenosine may be part of the start codon of an untranslated ORF (uORF) in the human Sodium-dependent phosphate transporter 2 protein (SLC20A2).

The invention discloses a modified linear arRNA (Ribonucleic Acid) or cyclized arRNA and an application of the modified linear arRNA or cyclized arRNA in RNA (Ribonucleic Acid) editing. The invention provides an RNA (referred to as a modified arRNA), comprising n copies of arRNA truncated bodies; and n is a natural number greater than 2. The modified arRNA can be a linear RNA (Ribonucleic Acid) or a circular RNA (Ribonucleic Acid). To minimize the effect of bystanders without reducing the editing efficiency. The RNA sequence structure is modified by minimizing the specific sequence, the recruitment structural domain is combined, and the cyclization mechanism is optimized. Compared with the existing ADAR technology, the method and the device have the advantage that the editing efficiency is remarkably improved.

The present invention relates to the field of diseases caused by high LDL-C and / or fibrinogen levels, such as cardiovascular diseases. The invention relates to oligonucleotides for RNA (Ribonucleic Acid) editing technology. The oligonucleotides are used for deamination of target adenosine nucleotides, such as 1055th adenosine, in human B4GALT1 gene transcripts.

The invention belongs to the technical field of gene editing, and particularly relates to a crRNA and CRISPR / Cas reagent and application thereof, and the crRNA and CRISPR / Cas reagent is suitable for RNA editing of a Qianzebra fish rasd1 gene. The crRNA has a sequence as shown in SEQ ID NO. 1, SEQ ID NO. 2 or SEQ ID NO. 3. The crRNA provided by the invention can be used for accurately identifying the rasd1 gene locus of the zebrafish in a targeting manner, so that zlwacas13a is more accurate when knocking down the rasd1 gene of the zebrafish.

The disclosure relates to the field of chronic pain and the treatment thereof. The disclosure involves antisense oligonucleotides and the use thereof in pre-mRNA and mRNA modulation, in one aspect related to RNA editing using endogenous ADAR enzymes, in targeting an adenosine in a (pre-) mRNA for human Nav1.7, preferably to change from a lysine residue to an arginine residue in the protein at position 1406 (K1406R), thereby impairing the ability of the Nav1.7 protein to act as a sodium ion channel. In another aspect the disclosure relates to exon skipping wherein antisense oligonucleotides are used to induce skipping of exon 23 in the generation of human SCN9A mRNA thereby generating a shortened Nav1.7 protein with an impaired ability to act as a sodium ion channel. The disclosure relates to methods and means to alter the Nav1.7 protein in cells of the peripheral nervous system, preferably large nociceptor cells (type Aα / Aβ), to provide a treatment of chronic pain.

The present invention relates to the field of RNA editing using novel Cast 3 polypeptides in a CRISPR / Cas13 system. The novel Cast 3 polypeptides have collateral, or ‘trans’ cleavage activity and can be utilised in a nucleic acid detection systems, such as a Cast 3 SARS-CoV-2-based detection assay.

Disclosed are methods and compositions for promoting trans-splicing. In some embodiments, the composition comprises an engineered small nuclear RNA that promotes trans-splicing of a target RNA molecule. The composition may further comprise an RNA donor molecule.

SnRNA systems comprising RNA binding sequences for RNA editing are disclosed herein.