178 results about "Protein translation" patented technology

Methods and compositions for modulating repeat non-ATG protein (RAN protein) translation are provided. In some aspects, the disclosure relates to methods for treating a subject having a disease associated with RAN protein translation by administering the subject a modulator of eIF3 or an eIF3 subunit, or an antibody that bind to a RAN protein.

The invention discloses a quinoa CqARF2 gene mutant as well as an identification method and application thereof. Chenopodium quinoa seeds are mutated on a large scale by utilizing a chemical mutagenic agent EMS, a CqARF2 gene function deletion mutant arf2 is adopted as a quinoa mutant, G at the 1050th site of the CqARF2 gene of the mutant is mutated into A, and amino acid at the 350th site is mutated into a termination codon, so that the translation process of CqARF2 protein is terminated in advance. The chenopodium quinoa CqARF2 gene function deletion mutant arf2 shows remarkable agronomic character improvement, seeds are large and full, compared with a wild type, the hundred-grain weight of the mutant seeds is increased by about 40%, the seed diameter is increased by about 10%, the seed thickness is increased by about 30%, and a certain foundation is laid for breeding new high-yield and high-quality chenopodium quinoa varieties.

Methods and compositions for modulating repeat non-ATG protein (RAN protein) translation are provided. In some aspects, the disclosure provides methods of inhibiting RAN protein translation by contacting a cell with an effective amount of an inhibitor of eIF2 phosphorylation or an inhibitor of protein kinase R (PKR). In some embodiments, methods described by the disclosure are useful for treating diseases associated with RAN protein translation, such as certain neurodegenerative diseases.

The invention discloses a corn ZmMYBR37 gene and an application of the corn ZmMYBR37 gene in regulating and controlling the size of corn kernels. The nucleotide sequence of the ZmMYBR37 gene is as shown in SEQ ID No: 1 in a sequence table. A mutant material with small grains and reduced hundred-grain weight is separated from a corn EMS mutant library, and a mutation site occurs on a function unknown gene ZmMYBR37, so that protein translation is terminated in advance. The information analysis finds that the gene coding protein has a conservative MYB structural domain, and the gene coding protein is speculated to belong to an MYB transcription factor family. Gene expression analysis finds that the gene is high in constitutive expression in corn and high in expression level in leaves and embryos. The corn material overexpressed with the ZmMYBR37 has the advantages that the grain size is increased, and the hundred-grain weight is obviously increased, so that the ZmMYBR37 has the potential of increasing the corn yield.

The invention belongs to the field of bioinformatics, and relates to a protein post-translational modification prediction method based on multi-modal deep learning. The method comprises the following steps: firstly, performing multi-modal feature extraction by inputting a protein sequence and three-dimensional structure data to obtain a sequence feature vector and a structure feature vector; secondly, carrying out feature fusion by adopting a cross-modal attention mechanism and a self-adaptive gating network; then, combining the fusion features with the disease type information, and performing fine adjustment on the prediction probability through a disease specific coding network; then, using a multi-task learning framework to predict the locus probabilities of various protein post-translational modification types in parallel; finally, feature importance is calculated through a gradient back propagation technology, and a comprehensive report is output in combination with variation influence analysis. According to the method, high-precision and explainable protein post-translational modification prediction with disease perception capability is realized, and an important calculation and analysis tool is provided for revealing a disease molecular mechanism and finding accurate drug targets.

The invention provides a novel IRES sequence suitable for circular RNA and a variant and an untranslated region sequence of the IRES sequence. The invention provides a circular RNA drug containing the IRES sequence, the untranslated region sequence and the protein coding sequence. The circular RNA drug platform has efficient protein translation ability (especially in immune cells), simplified sequence length and compatibility to various protein sequences, and the drug based on the circular RNA platform shows a good treatment effect in an animal tumor model.

The invention discloses a multispectral intelligent identification system for protein post-translational modification sites, comprising: a spectral data acquisition module for controlling different spectrum analyzers to perform spectrum scanning and analog-to-digital conversion and formatting on protein samples in parallel to obtain multiple protein multispectral original data; the intelligent analysis module is used for carrying out preprocessing and feature extraction on the multi-spectral original data of each protein to obtain a plurality of standardized spectral feature vectors; fusing each standardized spectral feature vector to obtain a multi-dimensional feature vector, inputting the multi-dimensional feature vector into a pre-trained modification site recognition deep learning model, and outputting a recognition result list, the recognition result list comprises the positions of the recognized protein post-translation modification sites in the protein sequence and modification types corresponding to the protein post-translation modification sites; and the result output module is used for visually displaying and exporting the identification result list. According to the method, the accuracy and flux of protein post-translational modification site recognition are remarkably improved.

The invention discloses a saccharomyces cerevisiae recombinant strain based on a uracil metabolism gene URA3 as well as a construction method and application of the saccharomyces cerevisiae recombinant strain. The construction method comprises the following steps: taking saccharomyces cerevisiae rich in farnesyl pyrophosphate as an original strain, introducing a uracil metabolism gene URA3, synchronously overexpressing a ribosome biosynthetic gene UTP10 and an iron metabolism gene FIT3, and utilizing the uracil metabolism gene URA3 to express up-regulation correlation with the ribosome biosynthetic gene UTP10 and the iron metabolism gene FIT3, so as to obtain the farnesyl pyrophosphate-rich saccharomyces cerevisiae. The metabolic flux of the terpenoids is enhanced, and the saccharomyces cerevisiae recombinant strain for efficiently producing the terpenoids is constructed. According to the method, a metabolic network of yeast is systematically optimized, and combined regulation and control on precursor flux distribution, protein translation capability and metal ion steady state are realized, so that the microbial synthesis efficiency of sesquiterpenoids such as patchouli alcohol and beta-elemene is remarkably improved.

The invention relates to the field of biological medicine, and discloses application of a GADD34 inhibitor in preparation of a medicine for enhancing CAR-T cell tumor treatment. The invention provides an innovative strategy for inhibiting CAR-T cell depletion through targeted regulation and control of an endoplasmic reticulum stress pathway to solve the problems that in an existing CAR-T therapy, the anti-tumor activity is reduced, and the solid tumor treatment effect is insufficient due to T cell depletion. Researches find that an IRE1-XBP1 pathway is used as a core signal axis of endoplasmic reticulum stress, and excessive activation of the IRE1-XBP1 pathway can drive CAR-T cell depletion related phenotypes (such as PD-1 / LAG-3 up regulation and cytokine secretion reduction). Screening experiments show that inhibiting the upstream regulatory factor GADD34 of the IRE1 not only can effectively reduce the IRE1-XBP1 signal intensity, but also can cooperatively relieve the endoplasmic reticulum stress pressure by regulating protein translation recovery, so that the CAR-T cell steady state is more comprehensively maintained. Therefore, the GADD34 inhibitor can provide a new way for enhancing CAR-T cell tumor treatment.

In certain aspects, the invention relates to engineered inhibitory transport RNA (tRNA) molecules that restore translation of an encoding nucleic acid containing an advanced UGA / TGA termination codon by inserting arginine (Arg) into a polypeptide when decoding the UGA / TGA termination codon. In addition, the invention also encompasses expression cassettes and vectors comprising nucleic acids encoding the engineered inhibitory tRNAs, as well as compositions containing these expression cassettes, vectors and / or engineered inhibitory tRNAs, as well as methods involving the engineered inhibitory tRNA molecules for the recovery of protein translation and / or the treatment of disease.

The invention provides a method for improving the genetic stability of PolyA tail of mRNA (messenger ribonucleic acid). The method for improving the genetic stability of the PolyA tail in the preparation process of the mRNA containing the PolyA tail comprises the steps that a plasmid vector containing three-segment PolyA polynucleotides A1-G-A2-G-A3 is transferred into a host cell to be cultured, A1, A2 and A3 are each independently composed of 30-45 continuous A, and the host cell is selected from DH5a, Stbl3 and JM109; and separating and recovering a plasmid vector containing PolyA polynucleotide, carrying out enzyme digestion linearization to obtain an mRNA transcription template, and carrying out transcription to prepare mRNA. According to the method, the high genetic stability of the plasmid PolyA tail sequence can be achieved, the stability of mRNA is not affected, the mRNA protein translation efficiency is not affected, and the Oligo-dT purification process is not affected.

The invention relates to the field of pharmaceutical chemistry, and in particular to a conjugate of a protein translation inhibitor and use thereof in preparing a drug for treating and / or preventing a disease.

This invention discloses a phosphorylated diamine morpholino oligonucleotide drug that regulates PAPOLA expression and its application, belonging to the field of biomedical technology. The nucleotide sequence of the drug is shown in SEQ ID NO:1, targeting the coding region of human PAPOLA mRNA. The formulation is a lyophilized powder for injection, with excipients including mannitol and phosphate buffer. This invention also discloses the application of this drug in the preparation of a treatment for gastric cancer, specifically advanced gastric cancer with high PAPOLA expression. The drug is administered intravenously at a dose of 8-12 mg / kg every 3 days. Its mechanism of action is to block PAPOLA protein translation, inhibit the G1 / S phase transition of gastric cancer cells, and induce apoptosis. In vitro and in vivo experiments have confirmed that this drug can specifically inhibit the proliferation and growth of gastric cancer cells, providing a new treatment option for advanced gastric cancer.

Provided herein are recombinant circular RNA (circRNA) molecules comprising an internal ribosome entry site (IRES) operably linked to a protein-coding nucleic acid sequence. The IRES may be, for example, a Type I IRES, such as a viral IRES. In some embodiments, the IRES is a synthetic IRES, such as an IRES comprising an aptamer. Methods of producing a protein in vitro or in vivo using the recombinant circRNA molecules are also provided.

The present invention provides targeting polyplexes comprised of (i) nucleic acids, in particular nucleic acids encoding pharmaceutically active peptides or proteins, and (ii) targeting conjugates comprising LPEI and PEG fragments that are connected by discrete linkages formed through defined, chemoselective reactions. Thus, the LPEI fragment is bonded in a linear end- to-end fashion to a single PEG fragment. The linear conjugates are further conjugated to a targeting fragment to enable selective interaction with a particular cell type. The polyplexes selectively deliver the nucleic acids to the targeted cells resulting in high expression and efficient protein translation as well as secretion of the encoded pharmaceutically active proteins.

The invention belongs to the technical field of bioengineering, and particularly relates to an in-vitro transcription vector with a long poly A tail and capable of being stably copied and application of the in-vitro transcription vector. The in-vitro transcription vector comprises a promoter element, a 5 'UTR element, a target protein gene sequence, a 3' UTR element and a poly A tail element, the length of the poly A tail element is 50-180 A basic groups, the poly A tail element can protect a cap structure from being degraded, and the poly A tail element cooperates with poly A binding protein, 5 'Cap (cap structure) and translation initiation factor protein to initiate protein translation. The in-vitro transcription vector prepared by the invention can be stably passed in Escherichia coli, avoids deletion of tail A, has high stability and long-acting expression, is beneficial to subsequent protein purification and functional research, and is suitable for long-term experiments.

The invention belongs to the technical field of biological medicines, and particularly relates to a granzyme B expression system as well as a preparation method and application thereof. According to the invention, granzyme B with bactericidal activity is screened out, a corresponding expression vector is designed by adopting circular RNA, a bacterium-specific ribosome binding site (RBS) is taken as a protein translation regulation and control element, and a Lipid nano-particle (LNP) is taken as a delivery vector, so that efficient delivery of the circular RNA for coding GZMB and specific expression of GZMB in bacteria are realized. According to the strategy, efficient delivery and specific expression of circRNA for coding GZMB in bacteria are achieved, and a safe and accurate scheme is provided for GZMB antibacterial treatment.

To provide a method for producing a protein that self-proliferates an energy-regenerating enzyme.SOLUTION: The problem can be solved by a method for producing a protein, the method comprising a protein translation step for translating a protein using a translation template mRNA in the absence of a cell and in the presence of an element for translating the translation template mRNA into the protein, wherein the translation template mRNA includes a translation template mRNA for translating an energy-regenerating enzyme.SELECTED DRAWING: None

This invention belongs to the field of bioinformatics and relates to a method for predicting protein post-translational modifications based on multimodal deep learning. First, multimodal feature extraction is performed on the input protein sequence and 3D structural data to obtain sequence feature vectors and structural feature vectors. Second, a cross-modal attention mechanism and an adaptive gating network are used for feature fusion. Then, the fused features are combined with disease type information, and the predicted probabilities are fine-tuned using a disease-specific coding network. Next, a multi-task learning framework is used to predict the site probabilities of various protein post-translational modification types in parallel. Finally, gradient backpropagation is used to calculate feature importance, and a comprehensive report is output based on variation impact analysis. This invention achieves high-precision, interpretable, and disease-aware protein post-translational modification prediction, providing an important computational analysis tool for revealing the molecular mechanisms of diseases and discovering precise drug targets.

The present invention pertains to the field of protein engineering, molecular imaging, molecular diagnostics, and biopharmaceutics. Provided herein are six unique Proteimer protein scaffolds (TEX-S2 / S3, TEX-S4, YTHDF3, PUM, DARPin, and Aca2) that demonstrate specificity and affinity comparable to antibodies across a broad range of therapeutic targets. Methods and protocols are provided for generating non-native protein aptamers, Proteimers, which are capable of binding to a diverse set of targets, including RNA, DNA, proteins, post-translational modifications, peptides, small molecules, and prosthetic groups. This platform supports the creation of biotherapeutic aptamers from Proteimer scaffolds for the treatment of various diseases.

The invention belongs to the field of biology, and particularly relates to construction of a recombinant Seneca virus strain with Seneca virus 2B protein translation block site mutation. The 26th lysine (K) of the 2B protein is found to be a key site for inhibiting the translation of the host protein for the first time, and after the 26th K of the 2B protein is mutated into the alanine (A), the translation retardation phenomenon of the host protein is obviously weakened; secondly, the 26th K of the 2B protein is mutated into A to construct infectious clone, and the recombinant Seneca virus strain rSVA-2B K26A with 2B protein translation retardation site mutation is successfully rescued and obtained, compared with wild type SVA, after the rSVA-2B K26A infects host cells, the translation retardation phenomenon of the host cells is weakened, the expression level of host antiviral inflammatory cytokines is enhanced, and the expression level of the recombinant Seneca virus strain rSVA-2B K26A is improved. The Seneca virus vaccine strain can be used as a potential vaccine candidate strain, and a foundation is laid for developing a novel prevention and control strategy aiming at the Seneca virus.

The present disclosure relates to compositions and methods to modulate the level of expression of a protein in a deliberate manner (i.e., tunable regulation of expression) with only a minimal change to the genetic sequence of the gene of interest. The present disclosure therefore also provides compositions and methods to predictably alter protein abundance.

A toehold exchange riboregulator gate includes: a gate input toehold domain; a ribosome binding sequence; a start codon; a c spacer domain positioned between the ribosome binding sequence and the start codon; a protein coding sequence; and a self-cleaving ribozyme sequence that produces a double-stranded RNA gate suitable for strand exchange and produces the gate input toehold domain.

Provided herein are engineered expression cassettes for expressing a transfer RNA (tRNA), wherein the expression cassette is a DNA comprising a 5' flanking sequence, a nucleic acid encoding the tRNA, and a 3' flanking sequence, and wherein neither the 5' flanking sequence nor the 3' flanking sequence contain a promoter driving expression of the tRNA. Also provided are plasmids or vectors comprising an engineered expression cassette, pharmaceutical compositions comprising the expression cassettes, vectors, and / or an engineered tRNA produced by such cassettes, and methods of restoring protein translation and / or disease treatment involving using an engineered expression cassette to produce engineered tRNA molecules.

The present invention relates to the field of pharmaceutical chemistry, and in particular to a protein translation inhibitor as represented by formula (II) and a use thereof in treatment and / or prevention of diseases.

The invention provides a porcine low-sugar FSH (follicle stimulating hormone) recombinant protein, a recombinant expression vector and a preparation method of the porcine low-sugar FSH recombinant protein. The amino acid sequence of the swine low-sugar type FSH recombinant protein is as shown in SEQ ID NO. 1, SEQ ID NO. 2, SEQ ID NO. 3 or SEQ ID NO. 4. The invention also discloses a preparation method of the swine low-sugar type FSH recombinant protein. According to the novel swine low-sugar type FSH carrier obtained through genetic engineering, N-glycosylation motif Asn-X-Thr mutation is introduced, and N-glycosylation modification after protein translation is artificially regulated, so that stable and efficient expression of the low-sugar type FSH is realized, and the biological activity of the low-sugar type FSH carrier is also greatly improved.

Methods and compositions for modulating repeat non-ATG protein (RAN protein) translation are provided. In some aspects, the disclosure relates to methods for treating a subject having a disease associated with RAN protein translation by administering the subject a modulator of eIF3 or an eIF3 subunit, or an antibody that bind to a RAN protein.

The invention discloses application of a triple-helix structural element in RNA (Ribonucleic Acid) drug design, and belongs to the field of biological medicines. According to the application, an ENE element or a mutant of the ENE element is used as a nucleic acid stabilizing element, and the interaction between 3 'UTR and poly (A) is optimized, so that the mRNA stability is enhanced, and the protein translation efficiency is further improved, and therefore, the problem of low protein expression quantity in RNA therapy is effectively solved. The mRNA sequence optimization strategy provided by the invention provides a new method for vaccine design in the field of infectious disease and tumor immunotherapy, and has a wide application prospect.

The present application generally relates to a method of treating advanced hepatic fibrosis with Formulation (I). Formulation (I) is a retinoid-conjugated lipid nanoparticle (LNP) containing HSP47 siRNA which prevents HSP47 protein translation.

The present invention discloses a co - culture of Bifidobacterium bifidum and macrophages, a preparation method and an application, belonging to the field of biotechnology. The co - culture of Bifidobacterium bifidum and macrophages of the present invention is the product after co - culturing Bifidobacterium bifidum BD - 1 and macrophages. A preparation method of the co - culture of Bifidobacterium bifidum and macrophages disclosed by the present invention comprises the following steps: co - culture the bacterial suspension of Bifidobacterium bifidum BD - 1 and the macrophage suspension, then centrifuge and take the supernatant to obtain the product. The present invention discloses the application of the above co - culture in the preparation of products for promoting the growth and development of nerve cells. The co - culture of the present invention has an obvious promoting effect on the development indexes such as mRNA expression and protein translation of nerve cells, and can promote the morphological development of nerve cells.