19 results about "Untranslated region" patented technology

Disclosed herein are a messenger RNA (mRNA) comprising an open reading frame (ORF) encoding a protein of interest, a heterologous 5' untranslated region (UTR) and / or a heterologous 3' UTR for highly expressing the protein of interest. A method for synthesizing the mRNA and uses of the mRNA are also provided.

The application belongs to the technical field of animal genetic engineering, and particularly discloses a construction method of C1R gene humanized animal cells and animal models and application thereof. The construction method of the C1R gene humanized animal cells comprises the following steps: introducing a human C1R gene into non-human animal cells, so that the human C1R gene is expressed in the non-human animal cells to produce humanized C1R protein, and meanwhile, the expression of an endogenous C1ra gene in the non-human animal cells is reduced or eliminated. The application preferably adopts CRISPR / Cas9 gene editing technology to accurately insert a genomic sequence encoding a human C1R mature protein into a 2nd exon region of a mouse C1ra gene, while retaining a mouse source promoter, a 5' untranslated region (UTR) and a signal peptide sequence. A mouse cell or model capable of specifically interacting with an anti-human C1R antibody is successfully constructed.

The application relates to an mRNA untranslated region translation efficiency prediction method and device, computer equipment and a storage medium. The method comprises the following steps: extracting sequence features and structure features of an mRNA sequence to be predicted, the structure features being generated by encoding based on at least one of free energy change and secondary structure of the mRNA sequence to be predicted; inputting the sequence features and the structure features into a trained translation efficiency prediction model for prediction to obtain a translation efficiency prediction result of an untranslated region in the mRNA sequence to be predicted. The method can improve the accuracy of the mRNA untranslated region translation efficiency prediction result.

The application provides a method and system for generating and predicting the function of mRNA untranslated region sequence based on coding sequence. The method comprises: constructing a pre-training data set and a downstream task data set; using the pre-training data set to perform autoregressive training on the constructed conditional generation model to obtain a UTR sequence generation model; using the downstream task data set to fine-tune the UTR sequence generation model to obtain a downstream task function prediction model; generating candidate UTR sequences based on the UTR sequence generation model, and evaluating the generation ability of the UTR sequence generation model in the non-coding region sequence generation task; and predicting the function attribute of the UTR sequence based on the downstream task function prediction model, and evaluating the prediction ability of the downstream task function prediction model in multiple UTR related downstream tasks. The application considers the synergistic relationship between UTR and CDS in the UTR sequence generation process, and improves the efficiency and rationality of UTR sequence design.

Compositions and methods are provided for influencing expression of endogenous genes or alleles in plants only in a heteroallelic state, such as in hybrid crops, while retaining unaffected expression of the endogenous genes or alleles in a homozygous state, by editing untranslated regions of the endogenous genes through genomic editing techniques.

Methods of evaluating mRNA or cDNA are provided. Instead of evaluating the mRNA or cDNA as a whole, multiple distinct portions of the mRNA or cDNA (such as different exons or untranslated regions) are separately quantified. The separate quantities are then evaluated by a trained classifier, which converts the separate quantities to a composite score indicative of the expression level of the mRNA or corresponding cDNA.

This invention relates to a method for targeted design and optimization of the 5′ untranslated region (UTR) of mRNA based on generative language models and reinforcement learning. The method includes: constructing pre-training data for the 5′ UTR; obtaining a prediction task dataset; calculating the minimum free energy (MFE) corresponding to the pre-training data; constructing a generative language model and performing phased pre-training on the generative language model using the pre-training data and the MFE to obtain a generative model and a prediction task fine-tuning model; fine-tuning the prediction task fine-tuning model based on the prediction task dataset to obtain a functional prediction model; evaluating the generative model's generation capability in the 5′ UTR sequence generation task; and performing targeted optimization design of the 5′ UTR sequence based on a reinforcement learning framework, combining the generative model and the functional prediction model. This invention can efficiently generate 5′ UTR sequences with specific biological functions, providing strong support for functional mRNA design and showing broad application prospects.

Disclosed herein are a messenger RNA (mRNA) comprising an open reading frame (ORF) encoding a protein of interest, a heterologous 5′ untranslated region (UTR) and / or a heterologous 3′ UTR for highly expressing the protein of interest. A method for synthesizing the mRNA and uses of the mRNA are also provided.

This invention relates to the field of gene editing technology, specifically to a gene circuit-based specific gene expression system and module, a pharmaceutical composition, and its applications. The system includes a first vector and a second vector. The first vector includes a first expression cassette containing a cell-specific promoter, a coding sequence encoding a transcriptionally activated fusion protein, and a regulatory region sequence downstream of the coding sequence. The regulatory region sequence is configured to form a response element in the 3' untranslated region of the fusion protein's mRNA after transcription. This response element binds to a specific long non-coding RNA within the silenced cell, leading to the degradation of the fusion protein's mRNA. The second vector includes a second expression cassette containing an associated promoter that can be activated by the transcriptionally activated fusion protein, and a target gene downstream of the associated promoter. Advantages: This ensures that the target protein is expressed only in target cells and not in cancer cells, avoiding adverse effects on non-target cells or tissues, and reducing treatment risks and side effects.

A method for designing an mRNA vaccine includes receiving sequence information of a candidate mRNA vaccine, extracting an input sequence including a 25nt primer-binding sequence in a 5′ UTR (Untranslated Region) of the sequence information, a 50nt sequence of the 5′ UTR immediately before a CDS (Coding sequence) region, and a 30nt sequence after a start codon of a coding region, calculating secondary structure information for the input sequence, predicting translation efficiency of the candidate mRNA vaccine by inputting the input sequence and the secondary structure information into a pre-trained deep learning model, and, when the translation efficiency of the candidate mRNA vaccine is equal to or greater than a threshold, generating a final mRNA vaccine sequence by linking a sequence of an antigen protein to the sequence information of the candidate mRNA vaccine.

Provided herein are translational regulatory elements, including 5' and 3' UTRs and nucleic acid molecules (e.g., RNA molecules (e.g., mRNA molecules), DNA molecules) comprising one or more of the same. The disclosure further relates to pharmaceutical compositions comprising the same for the use in the expression of proteins in a subject, e.g., for treating diseases.

The present application relates to the technical field of mRNA vaccine, in particular to a multi-antigen tandem mRNA lung cancer vaccine and its application in the preparation of an anti-tumor drug, comprising an mRNA molecule and a lipid nanoparticle encapsulating the mRNA, the mRNA sequentially comprises a cap structure, a 5' untranslated region, an open reading frame, a 3' untranslated region and a polyA tail from 5' end to 3' end, the open reading frame encodes a fusion antigen protein, which sequentially comprises a signal peptide, a lung cancer shared mutant antigen module, a tumor associated antigen module and a MHC-I directed transport domain, each antigen fragment is connected by an AAY connecting peptide, and the lipid nanoparticle is composed of ionized lipids, cholesterol, auxiliary phospholipids and PEG-lipids. The present application takes into account antigen specificity and coverage, can efficiently release antigen epitopes, improve antigen presentation efficiency, strongly activate specific anti-tumor immunity, adapt a stable delivery system, and has a good application prospect in lung cancer treatment.

This invention discloses a siRNA or shRNA construct for inhibiting RSRC1 expression and its application, relating to the field of biomedical technology. It includes a specific nucleotide sequence targeting human RSRC1 gene mRNA; this specific nucleotide sequence can specifically bind to the coding region (CDS) or 3' untranslated region (3'UTR) of the RSRC1 gene, mediating the degradation or translational repression of RSRC1 mRNA, thereby reducing the intracellular expression level of RSRC1 protein; the construct is configured to block the direct interaction between RSRC1 protein and DVL2 protein, thereby inhibiting the activation of downstream Wnt / β-catenin signaling pathways and AKT / mTOR signaling pathways. This invention, while inducing tumor cell apoptosis, inhibiting colony formation, and reducing metastatic nodules in vivo, avoids the limitations of single-target silencing in completely blocking multi-pathway cross-talk, ultimately achieving a synergistic therapeutic effect of significantly reducing chemotherapy resistance, inhibiting metastasis of advanced ovarian cancer, and prolonging patient survival.

This disclosure provides methods and systems generally relating to predicting cell-type-specific activity of one or more untranslated region (UTR) RNA sequences and generating UTR RNA sequences with predefined cell-type-specific activity, in particular using machine learning models.

The application belongs to the technical field of biotechnology, discloses mRNA and a preparation method, use and vaccine thereof, a nucleotide sequence of a HA antigen coding gene of the mRNA is shown as SEQ ID NO:1, the mRNA is obtained by the following steps: adding a T7 promoter, a 5' end untranslated region and a Kozak sequence at the front end of a coding sequence of an HA protein of a swine influenza virus H1N2 after codon optimization, adding a 3' end untranslated region at the rear end, forming a DNA template sequence, and then obtaining the mRNA, and the vaccine prepared by using the mRNA has the advantages of good immunogenicity and strong protection.

The present disclosure relates to genome editing systems and components for targeting, editing, and / or modulating the expression of a target nucleic acid sequence of interest, e.g., an LDLR target nucleic acid sequence in the 3' untranslated region (UTR) of the gene encoding the LDLR protein. The present disclosure is also directed to methods and applications thereof in connection with the treatment and / or management of hypercholesterolemia.

The present application relates to a kind of 1,3-butanediol genetically engineered bacteria.The bacteria include the 5' end untranslated region (UTR) sequence that is artificially modified, which is the UTR sequence of the gene gltA encoding citrate synthase, and a constitutive promoter sequence is added before the artificially modified UTR sequence, which can enhance the accumulation of substrate acetyl-coa, reduce the acetyl-coa into the tricarboxylic acid cycle, and improve the yield of 1,3-butanediol.And by adding other genes to strengthen the synthesis of precursors, the chassis organism is further modified, and finally the obtained strain is a high-yield 1,3-butanediol genetically engineered bacteria.

The present invention provides artificial nucleic acid molecules comprising novel combinations of 5' and 3' untranslated region (UTR) elements. The nucleic acid molecules of the invention are preferably characterized by increased expression efficiency of the coding regions operatively linked to said UTR elements. The artificial nucleic acids can be used for the treatment or prophylaxis of various diseases. The invention further provides (pharmaceutical) compositions, vaccines, and kits comprising said artificial nucleic acid molecules. In addition, in vitro methods for preparing the artificial nucleic acid molecules according to the invention are provided.

The present invention provides oligonucleotides, their conjugates, salts, and pharmaceutical compositions that increase the expression of glucocerebrosidase (GBA) in cells, as well as methods for treating diseases associated with reduced GBA expression, including Gaucher disease and / or Parkinson's disease. The oligonucleotides may contain a sequence of bases complementary to the sequence of bases in the 3' untranslated region (UTR) of the GBA mRNA transcript.