113 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 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.

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 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.

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 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 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.

The invention relates to a chemically modified circular RNA (Ribonucleic Acid) molecule as well as a preparation method and application thereof. Specifically, the invention discloses a chemical modification method compatible with the annular mRNA, and the immunogenicity of the annular mRNA can be remarkably reduced and the stability and the protein translation level of the annular mRNA can be remarkably enhanced by containing the chemical modification. The circular mRNA containing chemical modification can significantly improve the patent medicine property of circular RNA and reduce toxic and side effects, has wide application in the fields of vaccines, protein delivery, cell therapy and the like, and has important significance in promoting the development process of circular RNA vaccines and drugs.

The application discloses a protein post-translational modification prediction method based on multi-head attention, and belongs to the technical field of biological information, and comprises the following steps: preprocessing protein sequences with post-translational modification annotation information to obtain a legal character set, a second protein sequence data set and a benchmark data set; obtaining three kinds of vocabulary tables based on the legal character set; performing multi-scale division on protein sequence samples in the second protein sequence data set to obtain a single amino acid scale data set, a dipeptide scale data set and a tripeptide scale data set; training a corpus by using a Skip-gram model structure to obtain three kinds of word vector models; performing label prediction on protein sequence fragments of the benchmark data set by using a multi-head attention model to obtain protein sequence fragment prediction results; and the multi-scale word vector is used to comprehensively utilize polypeptide composition information in the original protein sequence, and the dependence on biological feature engineering is reduced.

A conjugate of a protein translation inhibitor, and its use in the preparation of a medicament for the treatment and / or prevention of a disease, wherein the disease is a tumor or cancer.

The present invention belongs to the field of molecular biology technology, and specifically relates to a circular RNA expression vector, a construction method, and an expression method for a translatable protein. The present invention provides a circular RNA overexpression skeleton, comprising the following structures connected in sequence: an upstream homology arm sequence, an upstream cyclization-promoting sequence, a first restriction enzyme cleavage site, a spacer sequence, an IRES sequence, a second restriction enzyme cleavage site, a downstream cyclization-promoting sequence, and a downstream homology arm sequence. The circular RNA overexpression skeleton of the present invention can enable the expressed circular RNA to have protein translation ability, and the linear sequence of the gene to be cyclized is recombined into a eukaryotic expression vector loaded with an expression skeleton through the restriction enzyme cleavage site, and then the recombinant plasmid is transfected into the cell to enable the expressed target circular RNA molecule to translate protein. The circular RNA overexpression skeleton and expression vector constructed by the present invention provide a tool for expressing circular RNA with protein translation function.

This invention discloses a multispectral intelligent identification system for protein post-translational modification sites, comprising: a spectral data acquisition module, which controls different spectral analysis instruments to perform parallel spectral scanning of protein samples and performs analog-to-digital conversion and formatting to obtain various raw multispectral data of proteins; an intelligent analysis module, which preprocesses and extracts features from each type of raw multispectral data of proteins to obtain various standardized spectral feature vectors; fuses each standardized spectral feature vector to obtain a multidimensional feature vector and inputs it into a pre-trained deep learning model for modification site identification, outputting a list of identification results, which includes the location of the identified protein post-translational modification sites in the protein sequence and the modification type corresponding to each protein post-translational modification site; and a result output module, which visualizes and exports the list of identification results. This invention significantly improves the accuracy and throughput of protein post-translational modification site identification.

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.