976 results about "Effector" patented technology

Some aspects of this disclosure provide strategies, systems, reagents, methods, and kits that are useful for the targeted editing of nucleic acids or the modification of nucleic acids or proteins, including editing a single site within the genome of a cell or subject, e.g., within the human genome. In some embodiments, fusion proteins of nucleic acid programmable DNA binding proteins e.g., GeoCas9 or variants thereof, and effector domains, e.g., deaminase domains, are provided. In some embodiments, methods for targeted nucleic acid editing or protein modification are provided. In some embodiments, reagents and kits for the generation of targeted nucleic acid editing proteins, e.g., fusion proteins of a GeoCas9 and effector domains, are provided.

Described herein are polypeptides and related antibodies comprising a variant Fc domain. The variant Fc domain provide for stabilized Fc:Fc interactions when the polypeptide(s), antibody or antibodies are bound to its target, antigen or antigens on the surface of a cell, thus providing for improved effector functions, such as CDC-response.

The invention belongs to the field of gene engineering, and relates to a DNA binding protein based on TraC effect protein, a fusion protein with a cytosine / adenine base editing function, an editing system and nucleic acid molecules or constructs for encoding the DNA binding protein and the fusion protein. The invention also relates to complexes and kits for gene editing comprising the fusion proteins of the invention or the nucleic acid molecules encoding them. The base editing tool disclosed by the invention can realize efficient, accurate and safe base editing in cells of various eukaryotes such as animals and plants. The unique characteristics of the base editing tool enrich the types of existing base editing tools, and the base editing tool has wide application prospects.

The technology described herein relates to novel CRISPR / Cas systems and components thereof, vectors, proteins, fusion proteins, ribonucleoprotein complexes and methods of using the novel systems and components. The new system can be used in CRIS PRi applications and can be fused with any number of effector domain patterns, such as nuclease, base editor, leader editor, and the like, to conduct a variety of DNA modifications.

The invention belongs to the field of prevention and treatment of tilletia controversa Kuhn, and particularly relates to a tilletia controversa Kuhn effect protein g16561 and application thereof. An amino acid sequence of the Tilletia controversa Kuhn effect protein is shown as SEQ ID NO: 2. The effect protein plays an important role in the process of inhibiting plant defense reaction, and has an interaction relationship with a wheat protein in the process of infecting wheat by Tilletia controversa Kuhn. According to the invention, the pathogenesis of Tilletia controversa Kuhn can be deeply researched, and the excavation of wheat disease-resistant genes and the cultivation of wheat disease-resistant varieties can be promoted.

The invention relates to the technical field of microbial genetic engineering, in particular to a method for improving cordycepin synthesized by saccharomyces cerevisiae and saccharomyces cerevisiae engineering bacteria. According to the invention, codon-optimized 2 '-carbonyl-3'-deoxyadenosine reductase gene and 3 '-adenosine monophosphate phosphohydrolase gene from cordyceps militaris are expressed by using plasmids, and then the plasmids are transformed into host cells to obtain the saccharomyces cerevisiae engineering bacteria. And inoculating a seed solution obtained by seed culture of the activated saccharomyces cerevisiae engineering bacteria into a fermentation culture medium containing a metabolic effector, and carrying out fermentation culture to synthesize cordycepin. Metabolic effectors (Cu < 2 + >, Fe < 2 + >, Mg < 2 + >, Zn < 2 + >, citric acid, cysteine, aspartic acid, glycine, VB1 and tea polyphenol) are added into a fermentation culture medium strain, and the variety and concentration of the metabolic effectors are optimized, so that the yield and synthesis efficiency of cordycepin are remarkably improved. By using the combination of the strain obtained by the invention and the optimal effector, the yield of cordycepin in a fermentation tank reaches 2.9 g / L.

Some aspects of this disclosure provide compositions, methods, systems, and kits for controlling the activity of RNA-programmable endonucleases, such as Cas9, or for controlling the activity of proteins comprising a Cas9 variant fused to a functional effector domain, such as a nuclease, nickase, recombinase, deaminase, transcriptional activator, transcriptional repressor, or epigenetic modifying domain. For example, the inventive proteins provided comprise a ligand-dependent intein, the presence of which inhibits one or more activities of the protein (e.g., gRNA binding, enzymatic activity, target DNA binding). The binding of a ligand to the intein results in self-excision of the intein, restoring the activity of the protein.

The present disclosure relates to compositions and methods for reducing expression of MYC gene in a cell. In some embodiments, an expression repressor comprises a targeting moiety that binds a MYC promoter, anchor sequence, or super-enhancer. In some embodiments, the expression repressor comprises an effector moiety that represses transcription or methylates DNA. Systems comprising two expression repressors are also disclosed. The compositions can be used, for example, to treat cancers such as HCC.

Provided herein are inhibitors of receptor tyrosine kinase effector, RAF, pharmaceutical compositions comprising said compounds, and methods for using said compounds for the treatment of diseases.

The invention relates to a ligand-effector moiety provided with at least one saponin and antibody-effector moiety provided with at least one saponin. An aspect of the invention is a composition comprising the ligand-effector moiety provided with at least one saponin or the antibody-effector moiety provided with at least one saponin of the invention. The invention also relates to an antibody-drug conjugate comprising covalently linked saponin and to an antibody-oligonucleotide conjugate comprising covalently linked saponin. An aspect of the invention relates to a pharmaceutical composition comprising the ligand-effector moiety provided with at least one saponin or the antibody-effector moiety provided with at least one saponin of the invention, and optionally further comprising a pharmaceutically acceptable excipient. The invention also relates to the ligand-effector moiety provided with at least one saponin or the antibody-effector moiety provided with at least one saponin, for use as a medicament. The invention also relates to the ligand-effector moiety provided with at least one saponin or the antibody-effector moiety provided with at least one saponin of the invention for use in the treatment or prophylaxis of a cancer.

Feline, canine, and equine antibody variants and uses thereof, as well as compositions and methods for improving therapeutic monoclonal antibodies by modulating immune effector functions and antibody variants using those methods and compositions.

The disclosure provides, for example, double stranded DNA (dsDNA) molecules comprising one or more chemically modified nucleobases. In some embodiments, the dsDNA molecule is circular and comprises a first strand and a second strand, wherein the first strand comprises one or more chemically modified nucleobases, and the second strand is free of chemically modified nucleobases. In some embodiments, the dsDNA molecule comprises a promoter sequence and an effector sequence that encodes an effector.

The invention belongs to the technical field of immunotherapy, and particularly relates to a method for improving NK cell functions by targeted inhibition of lactylation. The invention provides a method for improving functions of NK cells by targeted inhibition of lactylation, NK cell lactic acid transporters or modification enzymes in inhibition of the lactylation process are targeted, the modification enzymes are NK cell lactylation modification enzymes Writer or lactic acid coenzyme A synthetase, NK92MI lactylation modification is blocked, so that function depletion of the NK cells is reversed, and the NK cell function is improved. The function of the NK cell can be partially reversed by inhibiting the lactic acid modification, and the expression level of effector molecules of the NK92MI cell can be recovered.

Provided herein are combinations of first and second antibodies having modified Fc effector functions resulting from amino acid substitutions in the Fc region, the amino acid substitutions allow for co-dependent activation of effector functions such as CDC and / or ADCC. Also provided are combinations of first and second antibodies having agonistic activity or enhanced agonistic activity resulting from amino acid substitutions in the Fc region where the agonistic activity is co-dependent of both a first and second antibodies.

The invention provides for systems, methods, and compositions for targeting nucleic acids. In particular, the invention provides non-naturally occurring or engineered DNA-targeting systems comprising a novel DNA-targeting CRISPR effector protein and at least one targeting nucleic acid component like a guide RNA.

The invention discloses a method for synthesizing a protein-RNA compound in vivo for nucleic acid detection, and relates to the technical field of biology. The technical key points are as follows: a series of recombinant plasmids capable of realizing the simultaneous expression of CRISPR / Cas effect proteins [including all sgRNA-guided Cas proteins such as Cas9, Cas12 (a, b, g, f and the like), Cas13, Cas14 and the like] and crRNA / tracrRNA (sgRNA) thereof in a series of expression strains of escherichia coli and assembling in the escherichia coli body are constructed, wherein the recombinant plasmids can be used for realizing the simultaneous expression of the CRISPR / Cas effect proteins [including all sgRNA-guided Cas proteins such as Cas9, Cas12 (a, b, g, f and the like); according to the present invention, the His tag is added to the 3'end of the compound gene, such that the compounds can be purified by using the nickel column so as to be used for subsequent nucleic acid detection, and the CRISPR / Cas protein nucleic acid compound assembled in vivo has characteristics of high enzyme activity, high sensitivity and high specificity so as to create good conditions for the CRISPR system to establish the nucleic acid detection platform;

The invention provides an application of a compound Aldometanib in preparation of a medicine for preventing and treating immune-related adverse reactions and diseases. Based on the first discovered prevention and treatment effects of Aldometanib on fatal immune hepatitis, immune myocarditis, pneumonia and enteritis, the invention specifically discloses application of Aldometanib in preparation of drugs for prevention and treatment of immune-related adverse reactions and diseases, and the main mechanism is that Aldometanib activates immune cells AMPK, enhances catabolism of immune cells, promotes immune cell apoptosis, promotes immune cell apoptosis, and improves immune cell apoptosis. The anabolism of the immune cells is inhibited, so that the expression of effector factors of the immune cells is controlled, and inflammatory factor storm is inhibited. Aldometanib has the effects of preventing the occurrence of immune-related adverse reactions and diseases, and inhibiting the attack levels of the immune-related adverse reactions and diseases, so that non-lethal and lethal injuries caused by an immune system to body organs are reduced.

Provided are an anti-albumin antibody or an antigen-binding fragment thereof and the use thereof, and an anti-albumin nanobody with improved affinity or an antigen-binding fragment thereof. The anti-albumin antibodies or antigen-binding fragments thereof can bind to albumins from different species with high affinity. In addition, the anti-albumin antibody can be linked to a bioactive effector molecule to form a fusion construct without affecting the activity of the bioactive effector molecule.

The invention discloses an arabidopsis thaliana RK3 gene and application of S structural domain receptor kinase RK3 coded by the arabidopsis thaliana RK3 gene in improvement of plant disease resistance, and belongs to the technical field of plant genetic engineering. According to the application of the arabidopsis thaliana RK3 gene to improvement of plant disease resistance, the nucleotide sequence of the arabidopsis thaliana RK3 gene is shown as SEQ ID NO.1, the amino acid sequence of S structural domain receptor kinase RK3 coded by the arabidopsis thaliana RK3 gene is shown as SEQ ID NO.2, and further plants are selected from arabidopsis thaliana, oilseed rape, rice, tomatoes, potatoes, peanuts, soybeans, cotton, tobacco, cucumbers, watermelons and the like. The expression of the plant disease resistance comprises infection resistance to wild-type pseudomonas syringae, effector engineering strains thereof and botrytis cinerea. It is clear that the arabidopsis thaliana RK3 gene and the encoded protein thereof can remarkably enhance the infection resistance of plants to various pathogenic bacteria for the first time, disease prevention and control are achieved by activating the autoimmune system of the plants, and an effective path is provided for reducing chemical pesticide application and promoting agricultural green development.

Herein are antibodies or antigen-binding fragments specifically binding to GPRC5D. Additionally, monovalent antibodies or antigen-binding fragments specifically binding to GPRC5D are also included. The Fc region of these antibodies contains K248E and T437R mutations (designated as "RE mutations") per the EU numbering system. The described antibodies, expressed in host cells that lack fucosylation capabilities, exhibit enhanced antibody¬ dependent cellular cytotoxicity (ADCC) and enhanced complement-dependent cytotoxicity (CDC).

The invention relates to the technical field of nano-drug presentation systems, in particular to a TCR (T cell receptor) nano-vesicle antibody with both T cell redirection and immunosuppression reversal as well as a preparation method and application of the TCR nano-vesicle antibody. The TCR nano-vesicle antibody comprises a vesicle formed by a liposome and a cell membrane; tCR protein, a PD-1 antibody and a CD3 antibody are loaded on the vesicles. The nano vesicle antibody has the functions of T cell redirection and immunosuppression reversion; the difficulty of low stability of the soluble TCR is overcome; the polypeptide can be rapidly enriched in tumor tissues through tumor specificity TCR, and CD8 + T cells infiltrated by tumors are directly activated through an anti-CD3 antibody; depletion of T cells can be reversed through the PD-1 antibody on the surface, and the effector function of tumor infiltration CD8 + T cells is improved. The technical scheme can solve the technical problems that the TCR stability is not ideal and the immunosuppression state of the tumor microenvironment is difficult to overcome, and has ideal application and popularization prospects.

The present disclosure provides one or more engineered gene effectors and systems, compositions, and methods of use thereof, wherein the one or more engineered gene effectors can be used to effect regulation of a target gene in a cell (e.g., an endogenous target gene in a cell). The one or more engineered gene effectors can be operatively coupled to a heterologous endonuclease, such as a CRISPR / Cas protein.

The invention discloses an effect protein E56, a coding gene and application of the effect protein E56 to improvement of southern rust resistance of corn, and belongs to the technical field of agricultural biology. The amino acid sequence of the effector protein E56 is as shown in SEQ ID NO. 1. A reverse genetics method is utilized to analyze the Puccinia polystachys effect protein E56 gene, and the E56 gene is up-regulated in expression in the Puccinia polystachys infection process. The E56 gene is silenced by adopting a host-mediated gene silencing technology, and the toxic function of the E56 gene in the infection process of the southern rust disease is determined. A specific fragment of the E56 gene is cloned to an RNAi interference vector, a corn immature embryo is transformed by using an agrobacterium tumefaciens-mediated transgenic technology, and an obtained transgenic corn plant shows resistance to the corn southern rust disease. The E56-RNAi transgenic plant shows resistance to puccinia polypoda, so that the effect protein E56 can be used for creating a new strain for resisting the southern rust disease.

The invention relates to the field of nucleic acid editing, in particular to the technical field of regularly clustered interval short palindromic repeat (CRISPR). In particular, the invention relates to a mutant of a Cas effector protein, a fusion protein comprising the mutant, and nucleic acid molecules encoding the same. The invention also relates to complexes and compositions for nucleic acid editing (e.g., gene or genome editing). The invention also relates to methods for nucleic acid editing (e.g., gene or genome editing) using the proteins or fusion proteins comprising the invention. Compared with a wild type Cas protein, the Cas protein mutant disclosed by the invention has better activity, such as higher cleavage activity, stronger target site recognition capability and higher target sequence editing activity.

The invention relates to the technical field of antitumor drugs, in particular to a Ru (II) complex and a preparation method and application thereof, and the Ru (II) complex has a structure as shown in a formula I. The Ru (II) complex synthesized by the method disclosed by the invention not only has relatively high cytotoxicity, but also has good photodynamic antitumor activity. After the complex is illuminated, the efficiency of the complex entering cells in an active transportation mode can be accelerated, mitochondria and endoplasmic reticulum are targeted at the same time, mitochondrial membrane potential decline and endoplasmic reticulum stress are caused to form a dual organelle damage effect, immunogenic cell death is caused, the tumor microenvironment is adjusted, and the tumor cell immunogenicity is improved. The enrichment of dendritic cells (DCs) in tumor cells is realized, the chemotactic activity of effector T cells is improved, the proportion of CD4 < + > and Foxp3 < + > cell populations is reduced, and finally the anti-tumor immune response is activated. Meanwhile, the complex provided by the invention can also induce the cell to generate pan apoptosis, retard the cell cycle in the G2 / M period and enhance the effect of the complex in inhibiting tumor proliferation.

The present invention relates to polypeptides which are covalently bound to molecular scaffolds such that two or more peptide loops are subtended between attachment points to the scaffold. In particular, the invention describes peptides which are high affinity binders of membrane type 1 metalloprotease (MT1-MMP). The invention also describes drug conjugates comprising said peptides, conjugated to one or more effector and / or functional groups which have utility in imaging and targeted cancer therapy.

The invention relates to tilletia foetida, in particular to a tilletia foetida effect protein TlRlpA and application thereof. The invention provides a Tilletia foetida effect protein, and the amino acid sequence of the Tilletia foetida effect protein is shown as SEQ ID NO: 2, SEQ ID NO: 4 or SEQ ID NO: 6. The effector protein can effectively inhibit programmed death of plant cells induced by BAX, and plays an important role in inhibiting a plant defense reaction process. The invention lays a foundation for deeply researching the pathogenesis of the tilletia foetida, excavating the tilletia foetida-resistant gene of the wheat and developing the tilletia foetida-resistant wheat variety.

Provided herein are methods for reducing the likelihood and / or severity of peripheral neuropathy, anemia, and / or neutropenia in an individual being treated with an antibody-drug conjugate (ADC). Also provided herein are methods for increasing dosing amount and / or frequency of an antibody-drug conjugate (ADC) in an individual. In some embodiments, the methods comprise administering to the individual an effective amount of an ADC that comprises an antibody conjugated to a drug moiety via a linker, wherein the antibody comprises a heavy chain comprising a human Fc region with reduced or eliminated effector function. Compositions, uses, and kits related thereto are also provided.

The disclosure provides, for example, DNA molecules comprising at least one nucleotide with a macromolecule, small molecule, or reactive handle (e.g., click handle) appended to a phosphorothioate backbone. The disclosure also provides methods for making such DNA molecules, for example using click chemistry. In some embodiments, the DNA molecule comprises a sequence that encodes an effector (e.g., a therapeutic effector).

Antibodies, antigen-binding proteins and Fc-fusion proteins that comprise recombinant polypeptides containing a chimeric heavy chain constant region sequence are provided that bind to certain Fc receptors however have reduced effector functions. Methods of making constructs for expression of such chimeric Fc-containing antibodies, antigen-binding proteins and Fc-fusion proteins in cell systems, and methods of producing and isolating the chimeric Fc-containing proteins are provided.