94 results about "Amino acid replacement" patented technology

A CVB virus expression vector comprising a PIV5 W3A viral genome comprising a mutation at amino acid residue S157 or S156 of the P / V gene and a deletion of the small hydrophobic (SH) gene of the PIV5 W3A viral genome, wherein the amino acid substitution at amino acid residue S157 or S156 comprises a substitution of serine (S) with phenylalanine (F) or asparagine (N), and the SH gene has a deletion of the SH open reading frame or the entire SH gene transcription unit. The CVB virus expression vector expresses a heterologous polypeptide, including SARS-CoV-2 spike (S), and / or nucleocapsid (N) and / or membrane (M) proteins, RSV fusion protein (F), or other antigens.

A variant polypeptide of xylanase, and a fusion protein and an enzyme composition comprising the variant polypeptide, a recombinant host cell for production of the variant polypeptide, methods for using it and its use, is disclosed comprising an amino acid sequence having at least 79%, but less than 100% amino acid sequence identity with amino acids 1-191 of SEQ ID NO: 1, wherein the amino acid sequence has xylanase activity, at least one disulfide bridge between two Cys residues in the 1-191 amino acid region, and an amino acid substitution at the position 23 or 28, or at the positions 23 and 28, the positions corresponding to the positions 23 and 28 of the SEQ ID NO: 1.

Disclosed are compositions and methods for engineered DLL4 proteins. In one aspect, disclosed herein are engineered DLL4 proteins comprising a conservative amino acid substitution at a residue corresponding to residues 28, 107, 143, 194, and 206 as set forth in SEQ ID NO: 1 and further comprising at least one conservative amino acid substitution at residues 256, 257, 271, 280, 301, and 305 as set forth in SEQ ID NO: 1.

There is provided a mutant KLF protein that can induce reprogramming of a somatic cell at a higher efficiency than a KLF protein having a natural amino acid sequence. There is also provided a method for efficiently producing an iPS cell by using the mutant KLF protein. There is provided a mutant KLF protein having an amino acid substitution, or a peptide fragment thereof containing the amino acid substitution.

To provide a modified tyrosine phenol lyase having improved activity for catalyzing a reaction (tyrosine cleavage reaction) for producing phenol from tyrosine.SOLUTION: Provided is a modified tyrosine phenol-lyase comprising an amino acid sequence in which one or more amino acid substitutions are introduced into an amino acid sequence of a wild-type tyrosine phenol-lyase, wherein an activity of catalyzing phenol production from tyrosine is improved compared to the wild-type tyrosine phenol-lyase, wherein the modified tyrosine phenol-lyase has amino acid substitutions at any one or more positions selected from positions corresponding to positions 25, 75, 144, 391, 419, and 456 of the amino acid sequence of SEQ ID NO: SELECTED DRAWING: Figure 1

The application discloses a method for constructing a CRBN gene humanized mouse model, which comprises replacing a knockout region of a mouse CRBN gene with a knock-in region of a human CRBN gene, so that the CRBN gene humanized mouse model is constructed, and the CRBN gene of the CRBN gene humanized mouse model is subjected to amino acid substitution of S369C, V380E, I391V and E431D. The application replaces a key functional domain of a mouse endogenous CRBN gene with a corresponding sequence of a human CRBN gene, so that the mouse can express a functional human CRBN protein, thereby solving the problem of lack of sensitivity of a wild-type mouse to a CRBN-dependent drug. The model provides an ideal preclinical experimental platform for studying the efficacy, toxicity and mechanism of action of a CRBN-related drug.

Provided is a parent phytase variant, which relates to the technical field of protein engineering. The variant, relative to the parent phytase thereof, has one or more amino acid substitutions at positions corresponding to positions 295, 349, and 374 of SEQ ID NO: 1. Compared to the parent phytase, the variant has increased thermal stability.

This invention relates to the field of biomedicine, specifically providing a mutant thymosin α1 polypeptide and its applications. The mutant differs from natural thymosin α1 by substituting at least one amino acid at positions 15, 21, and 27, with preferred mutations including D15M, E21W, and E27R. Amino acid substitutions at these sites significantly improve the structural stability and in vivo pharmacokinetic properties of thymosin α1. Experimental results show that, while maintaining the main secondary structural features and overall thermal stability without significant degradation, the mutant improves serum stability and in vivo pharmacokinetic properties, exhibiting superior in vivo half-life and antitumor activity. This invention also provides nucleic acid molecules encoding the mutant, expression vectors, host cells, and pharmaceutical compositions containing the mutant, which can be used for the treatment of tumors, viral infections, and immune-related diseases.

The invention relates to variants of the alpha subunit of interleukin-2 receptor (IL2R) and interleukin-2 (IL2). In one embodiment, the IL2 variants described herein have amino acid substitutions at the region of IL2 that contacts the alpha (α) subunit of the heterotrimeric IL2 receptor complex, IL2Rαβγ, reducing its ability to bind and activate the heterotrimeric receptor complex. Conversely, the corresponding IL2Rα variants described herein have amino acid substitutions compensating for such reduced ability of IL2 variants to bind to and activate IL2Rαβγ, preferably at amino acid residues contacted by IL2 amino acid residues that are substituted in the IL2 variants described herein.

The invention relates to proteases exhibiting proteolytic activity and comprising an amino acid sequence that, over its total length, corresponds to the amino acid sequence specified in SEQ ID NO:1 by at least 70% and increasingly preferably by at least 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 90.5%, 91%, 91.5%, 92%, 92.5%, 93%, 93.5%, 94%, 94.5%, 95%, 95.5%, 96%, 96.5%, 97%, 97.5% and 98% is identical, wherein the protease, with reference to the numbering according to SEQ ID NO:1, has at least one amino acid substitution at at least one of the positions corresponding to positions 97, 3, 99, 127 and 211, which is selected from the group consisting of N97E, R99E, R99I, R99N, R99V, R99T, D127E and M211C. Such proteases are suitable for use in washing and cleaning agents, in particular liquid textile detergents, and exhibit improved cleaning performance compared to a reference protease.The invention further relates to the use of these proteases and processes in which they are used, as well as washing and cleaning agents containing them, in particular liquid textile detergents.

The invention relates to the technical field of genetic engineering, in particular to identification of a new insertion site of a self-assembled protein cage nanoparticle antigen epitope and application of the new insertion site in vaccine preparation. It is found that a foot-and-mouth disease virus antigen epitope is inserted between 62nd-63rd amino acids of an Encapsulin protein fragment after amino acid sequence modification, and / or the 62nd-63rd amino acids are replaced with the foot-and-mouth disease virus antigen epitope, efficient and soluble expression of a target antigen in escherichia coli can be achieved, and protein cage nano antigen particles are successfully self-assembled; the protein nano antigen particle can induce a widely neutralized anti-foot-and-mouth disease virus antibody, improves the immune efficacy, and has the potential of becoming a foot-and-mouth disease vaccine.

Provided herein are variant IgG4 Fc domains comprising amino acid substitutions that decrease self-interaction of a polypeptide and / or decrease aggregation.

This application relates to the fields of gene therapy and molecular biology. More specifically, the present invention relates to an isolated altered VP1 protein of adeno-associated virus serotype 5 (AAV5) capsid comprising one or more amino acid substitutions as compared to the VP1 protein of wild-type AAV5 capsid, which increase transduction efficiency, as well as to a capsid and a vector based thereon.

The present application relates to a Cas12 protein having an amino acid sequence set forth in any one of SEQ ID NOs: 1 to 104, or a functional fragment thereof, or having an amino acid sequence set forth in any one of SEQ ID NOs: 1 to 104 with one or more amino acid substitutions, insertions, and / or deletions, and a CRISPR-Cas system comprising the Cas12 protein, and use thereof.

The purpose of the present invention is to provide an immunogenic composition containing a new HBV polypeptide or polynucleotides encoding the polypeptide. The immunogenic composition contains at least one polypeptide selected from among polypeptides a) through c) or polynucleotides encoding the polypeptide, and can be used for treating or preventing HBV infection. a) an HBV surface protein polypeptide including a specific amino acid substitution; b) an HBV polymerase polypeptide including an inactivated reverse transcriptase domain and an inactivated ribonuclease H domain, and including a specific amino acid substitution; and c) an HBV core protein polypeptide including a specific amino acid sequence.

A dishwashing detergent may include a hydrogen peroxide source, a bleach catalyst, and a protease. The protease may include an amino acid sequence having at least 70% sequence identity to the amino acid sequence given in SEQ ID NO: 1 over its entire length and at least one amino acid substitution at at least one of the positions corresponding to positions 12, 43, 122, 127, 154, 156, 160, 211, 212, and 222, relating in each case to the numbering according to SEQ ID NO: 1.

The present invention provides interleukin 15 (IL-15) variants comprising amino acid substitutions for improved homogeneity as well as conjugates and fusion proteins comprising such IL-15 variants. Further, nucleic acids, vectors and host cells for expression of such IL-15 variants as well as pharmaceutical composition comprising such IL-15 variants are provided.

Disclosed herein are nucleic acid compositions and methods of use. The nucleic acid compositions may have a therapeutic nucleic acid sequence operably linked to a nuclear targeting sequence that increases expression of the therapeutic nucleic acid in a cell by at least 1.25 fold; at least 80% sequence identity to SEQ ID NO: 6; or a first regulatory element comprising a promoter sequence operably linked to a hemoglobin subunit gamma intron (hBGi) sequence, and a second regulatory element comprising a woodchuck hepatitis posttranscriptional regulatory element (WPRE) sequence. The nucleic acid compositions with these features may enhance therapeutic nucleic acid transfection and expression. Also disclosed herein are transgenes optimized for gene therapy applications, including novel FVIII transgene sequences, in which the B domain may be non-naturally occurring the A1 and / or A3 domain may include at least one amino acid substitution.

The application provides a Claudin 6 antibody containing a non-natural amino acid modification and a preparation method and application thereof, the sequence of the antibody is obtained by replacing original amino acids with non-natural amino acids on the basis of SEQ ID NO: 1 and 6; the replacement site of the non-natural amino acid is selected from any one or a combination of at least two of the following: heavy chain: S114, T115, P148, G156, A157, T159, Q191, V149, L158 or G161; or light chain: T109, A112, K169, S202, S203, L154 or S156. The application introduces non-natural amino acids into specific sites of the antibody and expresses the antibody by using a cell expression system, evaluates the influence of non-natural amino acid insertion at different sites on the expression level, structural stability and binding capacity of the antibody, and provides a new idea for rational design and functional optimization of the antibody.

Modified platelet-derived growth factor receptor alpha (PDGFRα) polypeptides are described. The modified polypeptides include at least one amino acid substitution that allows the polypeptide to retain the capacity to bind a cytomegalovirus (CMV) trimer comprised of glycoprotein H (gH), gL and gO, but leads to reduced binding to one or more platelet-derived growth factor (PDGF) ligands. Use of the modified PDGFRα polypeptides for inhibiting CMV replication and / or spread, or treating a CMV infection, is also described.

This invention discloses a protein sequence spatial compression and functional optimization method based on a large-scale model, belonging to the fields of artificial intelligence and proteomics. This invention mines potential amino acid substitution sites in consensus sequences and then controls the sequential substitution process using a large protein language model, thereby maintaining the functional stability of proteins during sequence substitution and subsequently screening for substitution combinations that effectively enhance protein function. Introducing a large protein model transforms protein sequences into embedding vectors representing protein structure, function, and physicochemical properties. By analyzing the embedding vectors during the substitution process, it is possible to prevent new proteins from deviating from their original function and basic structure due to substitution. This invention combines consensus substitution identification with large-scale model analysis, effectively compressing the sequence space of amino acid substitutions, thereby significantly improving the efficiency of protein design and modification.

Enhanced recombinant adeno-associated viruses (rAAVs) (e.g., rAAV2, rAAVrh8R, etc.) are provided herein for improved gene therapy of eye or central nervous system (CNS) disorders, wherein the rAAV comprises one or more amino acid substitutions that interact with the heparan sulfate proteoglycan. The invention provides methods for enhancing retinal cell transduction and methods for treating eye diseases with enhanced compositions of rAAV particles. Furthermore, enhanced recombinant adeno-associated viruses (rAAVs) (e.g., rAAV2, rAAVrh8R, etc.) are provided herein for improved gene therapy of CNS disorders. The invention provides methods for delivering the rAAV to the CNS, methods for treating CNS disorders with enhanced compositions of rAAV particles, and kits for delivering the rAAV to the CNS and / or treating a CNS disorder.

The invention relates to the technical field of biology, and discloses an influenza A virus H5 protein mutant and application thereof. In order to solve the problems of weak cross immune response to epidemic strains, insufficient stability of wild type HA protein, low immunogenicity and the like of the existing H5N1 vaccine, a stable soluble H5 protein mutant is constructed through a sequence modification strategy. Specifically, the 332th to 380th amino acids in the HA protein of a wild type influenza A virus H5N1 are replaced by SPGCAT, and point mutations T386C, L418P and H456P are introduced to obtain the mutant. The mutant can significantly improve the structural stability of trimer protein, improve the expression level of recombinant protein, broaden the cross protection spectrum, enhance the level of immunogenic hemagglutination inhibition antibodies and improve immune response balance.

Provided is a way to reduce the off-target effects of PPR proteins. The present invention is a modification method for PPR proteins. The method involves making a substitution at the amino acid at at least one of position 2 and position 13 of the amino acid sequence of one or more of the PPR motifs of a PPR protein that includes a plurality of PPR motifs. The amino acid substitution is, for example, at least one of a V2 substitution and a K13 substitution and, more specifically, at least one of a V2F substitution, a V2S substitution, a V2Y substitution, a K13Q substitution, and a K13S substitution.

The present invention relates to a synthetic phytase which comprises (a) the amino acid sequence as set forth in SEQ ID NO. 1, (b) a variant of (a) having at least 70% sequence identity to SEQ ID NO. 1, or (c) a fragment, fraction or shuffled variant of (a) or (b) maintaining phytase activity, with the proviso that the phytase comprises one or more amino acid substitutions at one or more positions relative to SEQ ID NO. 1 selected from the group consisting of V13, T30, N37, K45, L46, T81, N83, A89, A113, Q121, Q122, A123, H128, K131, K139, A142, H143, Q162, S164, A166, S170, Q182, N184, G186, K187, L188, A194, M195, A200, I201, N202, D204, N206, K207, A209, S218, T219, L225, H228, K234, N239, E243, S248, Q256, F257, M260, S261, N270, P288, P292, A311, A314, L319, S320, W321, K344, K347, M355, L359, Q365, P367, E372, T388, Q404, and N405.

The invention relates to the technical field of genetic engineering, in particular to Encapsulin fusion protein for expressing foot and mouth disease virus epitopes and application of the Encapsulin fusion protein in preparation of subunit vaccines. The invention discovers that different foot-and-mouth disease virus antigen epitopes are inserted among the 62nd to 63rd positions, the 124 to 125th positions, the 138 to 139th positions and the 239th to 240th positions of amino acids of an Encapsulin protein fragment subjected to amino acid sequence modification, and / or the 62nd to 63rd positions, the 124 to 125th positions, the 138 to 139th positions and the 239th to 240th positions of amino acids are replaced by different foot-and-mouth disease virus antigen epitopes; efficient and soluble expression of a target antigen in escherichia coli can be realized, and protein cage nano antigen particles are successfully self-assembled; the protein nano antigen particle can induce a widely neutralized foot-and-mouth disease virus antibody, improves the immune efficacy, and has the potential of becoming a broad-spectrum foot-and-mouth disease vaccine.

The present application provides a kind of human umbilical cord mesenchymal stem cell freeze-dried powder and its preparation method and application.The freeze-dried powder is prepared by stem cell and a composite protective agent containing trehalose, human serum albumin and recombinant Oligosarcus microlepidotus III type antifreeze protein mutant (rZaAFPIII-M) by specific programmed freeze-drying process. Among them, the rZaAFPIII-M is obtained by site-directed amino acid replacement, with improved stability and solubility. The technical scheme makes the obtained freeze-dried stem cells not only have high cell survival rate after recovery, but also can significantly maintain the ability of key paracrine repair factors and the biological activity to skin target cells, and the comprehensive effect is comparable to traditional cryopreservation. The product has good storage stability under refrigerated conditions, can be conveniently used in the preparation of skin tissue repair drugs or cosmetics with anti-aging and moisturizing effects, and provides a new solution for the standardization and industrialization of stem cell preparations.

The present application relates to the fields of gene therapy and molecular biology. More specifically, the present invention relates to an isolated modified capsid protein VP1 from adeno-associated virus serotype 9 (AAV9) comprising one or more amino acid substitutions compared to the wild-type AAV9 capsid protein VP1, which substitutions increase the efficiency of production (assembly) of the vector based on recombinant adeno-associated virus serotype 9 (rAAV9), to a capsid and a vector based on the above VP1, as well as to uses thereof.

The invention relates to proteases exhibiting proteolytic activity and comprising an amino acid sequence that is at least 70% identical over its total length to the amino acid sequence specified in SEQ ID NO:1, wherein the proteases, each with reference to the numbering according to SEQ ID NO:1, have at least one amino acid substitution selected from the group consisting of N121F, A194C, A209V, T218I, N237P, and N237W at at least one of the positions corresponding to positions 121, 194, 209, 218, and 237. Such proteases are suitable for use in detergents and cleaning agents, in particular textile detergents, and exhibit improved storage stability compared to a reference protease. The invention further relates to the use of these proteases and processes in which they are used, as well as detergents and cleaning agents containing them, in particular textile detergents.

Recombinant polypeptides comprising a modified ectodomain of a respiratory syncytial virus (RSV) fusion protein (F) are provided herein, wherein the ectodomain comprises a modified C-terminus alpha-helical segment and / or amino acid substitutions that stabilize the F protein in a prefusion conformation. A two-component protein nanostructure comprising a first trimeric component and a second pentameric component is also provided herein. A composition for use in vaccination, elicitation of an immune response, or treatment or prevention of RSV disease is provided herein.