6454 results about "Protide" patented technology

The invention relates to the improvement of endonuclease-based antimicrobials by blocking DNA repair of double-strand break(s) (DSB(s)) in prokaryotic cells. In this respect, the invention especially concerns a method involving blocking DNA repair after a nucleic acid has been submitted to DSB, in particular by a Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) associated programmable double-strand endonuclease. The invention particularly relates to the use of an exogenous molecule that inhibits DNA repair, preferably a protein that binds to the ends of the double-stranded break to block DSB repair. The invention also relates to vectors, particularly phagemids and plasmids, comprising nucleic acids encoding nucleases and Gam proteins, and a pharmaceutical composition and a product containing these vectors and their application.

The invention relates to a nano antibody targeting cadherin 17 and application thereof, and relates to the technical field of immunology and molecular biology, the amino acid sequence of a complementary determining region of the nano antibody targeting cadherin 17 comprises CDR1 shown as any one of SEQ ID NO: 21-32, CDR2 shown as any one of SEQ ID NO: 34-45, and CDR3 shown as any one of SEQ ID NO: 47-58. According to the invention, an alpaca immune phage display library is constructed, a series of nano antibody molecules targeting cadherin 17 (CDH17) are screened from the alpaca immune phage display library, and functions and applications of the nano antibody are verified at various levels of CDH17 antigen protein, CDH17 target cells, CDH17 CAR-T cells and the like.

The invention discloses a drug and target interaction prediction method based on multi-scale convolution feature fusion, which comprises the following steps: acquiring drug molecule data, target protein data and drug and target interaction data, constructing a drug molecule map according to the drug molecule data, and coding a target protein sequence according to the target protein data; inputting the drug molecular map into a model, and obtaining drug features through a multi-scale map convolutional network and a dynamic gating attention mechanism; inputting a target protein sequence into the model, and obtaining target features through hierarchical cavity convolution and a bidirectional gating cycle unit; through multi-head cross attention, the drug features are aligned with the target features, local and global cross-modal fusion is carried out, and drug target fusion features are obtained; based on the drug target fusion features, outputting a drug and target interaction prediction probability; and training the model according to the drug and target interaction data and the prediction probability, and applying the trained model to drug and target interaction prediction.

The invention relates to a high-activity recombinant XVII type collagen as well as a rapid preparation method and application thereof, and belongs to the technical field of bioengineering. The amino acid sequence of the high-activity recombinant XVII type collagen is as shown in SEQ ID NO. 1, and the nucleotide sequence of the high-activity recombinant XVII type collagen is as shown in SEQ ID NO. 2. The invention also provides a preparation method and application of the recombinant XVII type collagen. The high-activity recombinant XVII type collagen has good biological activity, has good effects of promoting cell adhesion, cell proliferation and cell migration, and can be compounded with other proteins to form raw materials of tissue engineering products, cosmetics, health care products or medicines. The high-activity recombinant XVII type collagen gene is integrated to different positions of a yeast genome through three different vectors, and the copy number of a target gene is increased, so that the expression quantity of the recombinant XVII type collagen is remarkably increased, and the yield of the high-activity recombinant XVII type collagen is effectively increased.

The invention relates to the technical field of computer-aided drug design, in particular to a drug molecule screening and optimizing method based on artificial intelligence prediction, which comprises the following steps: S1, obtaining a dynamic protein conformation set and molecular multi-dimensional characterization: obtaining a dynamic conformation set of a target protein and a physicochemical property spatial distribution diagram of a binding pocket of the dynamic conformation set, a two-dimensional molecular map topological structure and three-dimensional conformation coordinates of the drug molecules are obtained; s2, multi-modal fusion prediction is carried out; s3, generating interpretable optimization guidance; and S4, automatic iterative optimization: performing batch prediction and screening on the new candidate molecular structure, taking the screened optimal molecule as a new starting point, repeatedly executing the interpretability optimization guidance generation step and the step until an iteration termination condition is met, and outputting a final optimized molecule list. Through the multi-modal fusion deep learning model, the interaction strength of the drug molecules and the target protein can be quickly and accurately predicted, and the screening efficiency of the drug molecules is greatly improved.

The invention discloses a polypeptide and application thereof in preparation of a medicine for preventing and / or treating cancers. The amino acid sequence of the polypeptide is shown as SEQ ID No. 1 or SEQ ID No. 2. The cancer is at least one of breast cancer, colorectal cancer, leukemia, esophageal cancer, pancreatic cancer, brain glioma, kidney cancer, skin cancer, osteosarcoma, ovarian cancer and prostate cancer. The invention designs and synthesizes the polypeptide of a targeted staphylococcus tumor protein compound SND1-MTDH containing a nuclease structural domain 1 (SND1 and a heteromucin (MTDH), finds that the polypeptide has excellent inhibitory activity on various different types of human cancer cells for the first time, and provides an optional scheme for broad-spectrum anti-cancer drugs. The polypeptide applied in the invention is simple in synthesis process and low in production cost.

The invention discloses a drug resistance prediction method and system based on comparative learning and multi-modal fusion, and the method comprises the steps: firstly generating a molecular map and a molecular fingerprint based on the SMILES of a target drug, and extracting the molecular features of the drug through a comparative learning model constructed through combining a map attention network and a map convolution network; and then, acquiring protein expression, gene expression and metabolic expression data from the target tissue cells, extracting modal features through a deep convolutional network, a Transform encoder and a multi-dimensional attention network, and realizing adaptive fusion of the multi-modal features through a heterogeneous interactive attention mechanism. And finally, jointly inputting the fused multi-modal features and drug molecular features into a multi-layer sensor to realize high-precision prediction of the drug resistance of cells to drugs. By introducing a contrast learning and multi-modal feature fusion mechanism, the characterization capability and prediction precision of the model are effectively improved, and efficient and reliable support can be provided for drug screening and clinical decision making.

The invention provides for optimized binuclease fusion proteins with increased pharmacokinetic properties. The optimized binuclease fusion proteins of the invention two or more nuclease domains (e.g., RNase and DNase domain) operably coupled to an Fc domain. The invention also provides methods of treating or preventing a condition associated with an abnormal immune response.

The invention belongs to the field of molecular biology and immunology, and particularly relates to an anti-CD3 nano antibody capable of activating the activity of T cells as well as a preparation method and application of the anti-CD3 nano antibody. The invention provides a preparation method of the anti-CD3 nano antibody. The preparation method comprises the following steps: constructing a CD3 plasmid and an overexpression cell line, and immunizing alpaca to obtain peripheral blood mononuclear cells (PBMC) of the alpaca; extracting RNA (Ribonucleic Acid) and carrying out reverse transcription to obtain cDNA; carrying out PCR amplification on the antibody gene segment and cloning the antibody gene segment to a phage display vector; and electrically transforming the vector into SS320 competent cells to obtain the nano antibody library. After two rounds of panning, detecting and screening an antibody clone capable of being combined with the CD3 protein through ELISA (Enzyme-Linked Immunosorbent Assay); an antibody sequence is selected through sequencing, and an antibody protein is expressed by using a mammalian cell high-throughput expression system; and then detecting and screening the antibody which is only specifically combined with the CD3. The method disclosed by the invention is simple, convenient and rapid to operate, and can be used for preparing active antibodies for treating potential tumors and proliferative diseases.

The present disclosure provides compositions and methods for prime editing with improved editing efficiency and / or reduced indel formation with modified prime editors and prime editor fusion proteins. The disclosure further provides, vectors, cells, and kits comprising the compositions and polynucleotides of the disclosure.

The present invention belongs to the field of biopharmaceutical technology, and specifically relates to a method for preparing GLP-1 or its analogs. The present invention provides a leader peptide, and a fusion protein comprising the leader peptide. The leader peptide or fusion protein is used to prepare a semaglutide precursor polypeptide, and the results show that the yield of the prokaryotic expression fusion protein can reach 26g / L, and the purity of the precursor polypeptide obtained after enzyme cleavage is higher than 95%. The precursor polypeptide is further side-chain modified and connected with a dipeptide to efficiently prepare semaglutide.

The invention provides an UTR (Untranslated Region) element H2202 P1-G as well as a construction method and application thereof, and relates to the technical field of mRNA (messenger ribonucleic acid). According to the present invention, the ribosome load prediction and the secondary structure optimization are performed on the natural 5 'UTR of the HIV TAT 202 gene through the BaidleHelix platform, and the obtained HTAT 202 P1 sequence avoids the inhibitory hairpin structure so as to significantly improve the luciferase expression quantity compared to the natural UTR; an ncRNA sequence without a secondary structure is introduced on the basis of the HTAT 202 P1, translation inhibition of a 5 'cap region is further relieved, and the protein expression quantity of the constructed H2202 P1-G mutant (the DNA sequence of the H2202 P1-G is as shown in SEQ NO 1, and the RNA sequence is as shown in SEQ NO 2) is further improved.

The invention provides a high-stability recombinant humanized elastin, a genetically engineered bacterium for expressing the protein and application of the high-stability recombinant humanized elastin, and belongs to the technical field of binding tissue peptides. The nucleotide sequence of the recombinant humanized elastin is shown as SEQ ID NO.1; and the amino acid sequence is as shown in SEQ ID NO.4. According to the invention, the nucleotide sequence of the humanized elastin is subjected to codon optimization and transferred into escherichia coli to construct the genetically engineered bacterium for expressing the recombinant humanized elastin, so that the expression quantity of the recombinant humanized elastin can be increased, the stability of the recombinant humanized elastin can be improved, and the recombinant humanized elastin can be used for preparing the recombinant humanized elastin. The migration rate of the recombinant humanized elastin to the HSF cell is improved, and the expression quantity of the h-ELN gene, the h-COL1A1 gene and the h-COL3A1 gene of the HSF cell is improved.

The invention provides a drug target prediction method based on a 3D structure and a multilevel attention mechanism, and belongs to the technical field of drug target prediction. The technical problem to be solved is to provide a drug target prediction method based on a 3D structure and a multi-level attention mechanism. According to the technical scheme, the method comprises the following steps: collecting data information of an interaction tag among a related drug, a target sequence and a drug target protein, and processing and extracting SMILES character string characteristics of the drug; learning the numeralized protein amino acid sequence by using a convolutional neural network, completing feature coding of a target spot on the sequence through multi-layer convolution and pooling operation, and extracting target spot sequence feature data; a PDB file is read and modeled into a pocket graph, feature calculation is carried out on the pocket graph, a final protein structure representation code is generated, and structural feature data of target protein is extracted by modeling the PDB file; the method is applied to drug target prediction.

The specification provides programmable base editors that are capable of introducing a nucleotide change and / or which could alter or modify the nucleotide sequence at a target site in mitochondrial DNA (mtDNA) with high specificity and efficiency. Moreover, the disclosure provides fusion proteins and compositions comprising a programmable DNA binding protein (e.g., a mitoTALE, a mitoZFP, or a CRISPR / Casp) and double-stranded DNA deaminase that is capable of being delivered to the mitochondria and carrying out precise installation of nucleotide changes in the mtDNA. The fusion proteins and compositions are not limited for use with mtDNA, but also may be used for base editing of any double-stranded target DNA.

The invention relates to a fusion protein based on Cas12i3 and application of the fusion protein in mediating gene editing, the fusion protein is formed by fusing NLSSV 40, Cas12i3, NLS, IEE and XTEN, the amino acid sequence of the NLSSV 40 is shown as SEQ ID No. 3, the amino acid sequence of the Cas12i3 is shown as SEQ ID No. 5, the amino acid sequence of the NLS is shown as SEQ ID No. 7, the amino acid sequence of the IEE is shown as SEQ ID No. 9, and the amino acid sequence of the XTEN is shown as SEQ ID No. 11.

The invention discloses an RNA (Ribonucleic Acid) in-vitro cyclization and rolling circle translation method based on an I-type intron and an application of the RNA in-vitro cyclization and rolling circle translation method. According to the invention, a ribonucleic acid construct is obtained by splitting a specific non-complementary region of the I-type intron, and the preparation of'scarless' (traceless) circular RNA is realized through a ribozyme self-splicing principle and can be popularized to other I-type intron. By optimizing a splitting structure, high-efficiency cyclization can be realized without additionally adding GTP for catalysis under the condition of no homologous arm. Meanwhile, the original part of the ribonucleic acid construct is optimized, so that the cyclization efficiency is further improved. Particularly, a rolling circle translation (RCT) technical platform based on the CITE sequence is established, and the expression quantity of the protein or the polypeptide is greatly improved. Through verification, the cyclization and rolling circle translation method provided by the invention shows potential in vaccine and CAR treatment, and is expected to be used for clinical treatment of various diseases.

The invention discloses a double-layer microneedle patch and a preparation method thereof.The preparation method of the double-layer microneedle patch comprises the following steps that firstly, 3D printing is conducted through polydimethylsiloxane, and a PDMS mold similar to a machining microneedle is obtained; dispersing the medicine into the sericin solution to serve as an outer layer solution; dispersing germanium nanoparticles into the polycaprolactone solution to obtain an inner layer solution; and finally, adding the outer-layer solution into the needle-shaped groove of the PDMS mold, so that the needle-shaped groove is filled with the outer-layer solution, drying, adding the inner-layer solution, drying, and demolding to obtain the double-layer microneedle patch. When the double-layer microneedle patch is used for drug delivery, drugs can be dissolved and released in a short time, the inner layer is polycaprolactone (PCL) carrying photo-thermal agent germanium nanoparticles, degradation is slow, a photo-thermal effect is generated under irradiation of 808nm near-infrared light, residual tumor cells are induced to die immunogenicity, an immune microenvironment is programmed in a time sequence, and the double-layer microneedle patch has the advantages of being high in sensitivity, high in sensitivity and good in stability. Postoperative recurrence and metastasis of tumors are efficiently inhibited, and meanwhile operative wound repair is promoted.

The invention belongs to the field of biotechnology and medicine, and discloses mRNA (messenger Ribonucleic Acid) for coding luciferase and application thereof. The mRNA for coding the luciferase comprises an ORF sequence for coding the luciferase, and the ORF sequence for coding the luciferase is a nucleotide sequence as shown in one of SEQ ID NO: 10 to SEQ ID NO: 13. The invention provides a brand-new mRNA for coding luciferase, and the mRNA is stable in structure, not easy to degrade, high in translation efficiency, relatively high in protein yield, relatively high in biological availability and safety by reasonably optimizing a nucleic acid sequence of a functional region, can be applied as a reporter gene, and has good potential.

Among other things, the present disclosure provides designed DMD oligonucleotides, compositions, and methods of use thereof. In some embodiments, the present disclosure provides technologies useful for repairing mutant DMD transcripts by skipping exon 51 or exon 53, so that the transcript can be translated into an internally truncated but at least partially functional Dystrophin protein variant. In some embodiments, the present disclosure provides technologies useful for modulating DMD transcript splicing. In some embodiments, provided technologies can alter splicing of a dystrophin (DMD) DMD transcript. In some embodiments, the present disclosure provides methods for treating diseases, such as muscular dystrophy, including but not limited to Duchenne muscular dystrophy, Becker's muscular dystrophy, etc.

The present invention relates to the field of biochemistry, more particularly to proteomics, more particularly to protein sequencing, even more particularly to single molecule peptide sequencing. The invention discloses means and methods for single molecule protein sequencing and / or amino add identification using cleavage inducing agent. Said cleavage inducing agents which are not specific for one particular amino acid, cleave polypeptides step by step from the N-terminus onwards and provide information on the identity of the cleaved amino acids based on the kinetics of said reaction.

The invention belongs to the technical field of genetic engineering, and particularly relates to recombinant collagen based on engineering bacterium expression and a preparation method thereof, and the recombinant collagen is formed by connecting repetitive units derived from human III type collagen in series for three times; the invention also discloses a base sequence of the coding gene of the recombinant collagen, efficient expression and accurate folding of target protein are realized through genetic modification of engineering bacteria, a light-operated dynamic folding process and an orthogonal purification strategy, and cascade purification of a His6-SUMO tag and an intein-CBD module is utilized to obtain the recombinant collagen. The product purity and the native conformation retention rate are remarkably improved, and the technical problems that hydroxyproline depends on exogenous addition, the folding controllability is poor and the purification efficiency is low in a traditional process are solved.

Disclosed in the present invention are a KRAS G12D degradation agent as well as a preparation method therefor and the use thereof. The present invention provides compounds as shown below, and / or stereoisomers, enantiomers, diastereoisomers, atropisomers, deuterated compounds, hydrates, solvates, prodrugs and / or pharmaceutically acceptable salts thereof. The compounds provided by the present invention can effectively degrade and / or inhibit KRAS G12D protein in cells, and can be used for preparing drugs for treating and / or preventing related diseases or disorders caused by KRAS G12D mediation. G-L-E I

The invention provides a fluorescent protein selection marker staygold-ygjHr gene and application thereof, and belongs to the technical field of biological engineering. The preparation method comprises the following steps: replacing codons of L-valine in nucleotide sequences of a fluorescent protein gene Staygold and a gene ygjH by using a rare codon GTC to respectively obtain a fluorescent protein gene Staygoldr after codon replacement and a gene ygjHr after codon replacement, and connecting the two segments of genes after codon replacement by using a flexible protein peptide to obtain the fluorescent protein selection marker Staygold-ygjHr gene. Experiments prove that the gene can obviously improve the screening efficiency of L-valine high-yield strains.

The invention relates to the technical field of virus detection, and discloses a method for detecting salmon alphavirus in salmon based on RAA-CRISPRCas12a and application, the method comprises the following steps: dispersing a Cas12 protein solution, a guide RNA solution, an ssDNA reporter probe solution, a ribonuclease inhibitor, nuclease-free water and an RAA reactant in a buffer solution, incubating, and carrying out fluorescence intensity detection; the amino acid sequence of the Cas12 protein is as shown in SEQ ID NO. 5. The novel Cas12a protease with better cutting activity is used in the method, and can be successfully applied to detection of salmon alphavirus in salmons.

The invention discloses a colorectal cancer drug relocation method based on multi-omics integration. The system comprises a multi-omics data acquisition and preprocessing module, a tumor microenvironment analysis module, a specific disease network construction module, a multi-dimensional drug relocation module and a result evaluation module. And the tumor microenvironment analysis module comprises cell heterogeneity identification, cell map construction, cell annotation and tumor cell subset annotation. The specific disease network construction module comprises tumor feature expression program extraction, expression program screening, meta-program construction, clinical related meta-program recognition and specific disease protein interaction network construction. And the multi-dimensional drug relocation module comprises a module for identifying diseases by using a random walk algorithm, carrying out drug screening based on disturbance data, carrying out drug screening based on network proximity and carrying out comprehensive drug relocation. From the perspective of single cell data, element programs related to colorectal cancer survival are excavated, corresponding modules are designed, and the efficiency and precision of colorectal cancer targeted drug screening are improved.

The present invention discloses a pharmaceutical composition comprising a circular RNA and a drug delivery carrier. Compared with traditional linear 1 * siRNA and annular 1 * siRNA, the number of repeated series connection of positive-sense strands is increased to include but not limited to two or more, it is accidentally found that the silence effect is remarkably enhanced, the expression level of the PCSK9 gene can be remarkably reduced, and degradation of mRNA of PCSK9 protein is mediated. The nano-particles are used for delivering oligonucleotide, so that the stability is improved, the immunogenicity is reduced, the effects of lowering cholesterol, reducing aortic plaque load and resisting atherosclerosis are improved, and the nano-particles are safe and free of obvious liver and kidney toxicity and have a wide application prospect in the aspect of preparing medicines for treating hypercholesterolemia and coronary heart disease.

The invention is applicable to the technical field of drug research and development, and provides a lead compound discovery method based on a large language model, which comprises the following steps: determining a target spot and constructing an initial compound library; generating fragments and forming an initial fragment library; calculating the frequency of occurrence of the fragments and the affinity contribution degree of the fragments to the target protein, and updating the fragment library; fragment sampling weight calculation and candidate fragment selection; the large language model generates molecules according to the candidate fragments; evaluating the quality of the generated molecules and updating the molecule library; and repeating the cycle until a preset iteration round number is reached. A fragment-based drug design method is combined with the large language model, rich domain knowledge of the large language model is used for replacing human experts to guide drug design, fragments are used as prompts to stimulate the internal potential of the large language model, the advantages of the two methods complement each other, exploration of the whole chemical space is completed, and the drug design efficiency is improved. The lead compound reaching the human expert level is designed in actual use, and a new technical means is provided for drug research and development.

The invention relates to a drug delivery carrier based on extracellular vesicles and application thereof.The drug delivery carrier contains extracellular vesicle scaffold protein and recombinant membrane fusion protein, the recombinant membrane fusion protein comprises a first fragment and a second fragment, the amino acid sequence of the first fragment is shown as SEQ ID NO: 5, and the amino acid sequence of the second fragment is shown as SEQ ID NO: 6; the second fragment has n amino acids, the sequence of the second fragment is the sequence of the first n amino acids at the N end of the amino acid sequence as shown in SEQ ID NO: 7, and n is an integer between 50 and 200. According to the drug delivery carrier disclosed by the invention, the efficiency of releasing drug active molecules before reaching lysosome is remarkably improved, and the drug effect of extracellular vesicle drugs can be improved.