329 results about "Cell targeting" patented technology

The present invention relates to various molecular constructs having at least one cellular-targeting element, one protein-targeting element, and one ubiquitin ligase recruitment element, wherein these elements are conjugated in a manner that facilitates cellular uptake and targeted degradation of specific proteins within cells. The present invention further relates to multifunctional proteolysis-targeting chimera conjugates and uses thereof for the treatment of diseases or disorders such as immune and inflammatory diseases, infectious diseases, cardiovascular diseases, endocrine disorders, and various cancers that are otherwise resistant to traditional therapeutic regimens.

The present disclosure provides bispecific stealth lipid nanoparticle (LNP) compositions engineered to target specific tissues or cell-types, e.g., immune effector cells such as T cells, B cells, natural killer cells, and dendritic cells, to modify the cells with therapeutic nucleic acid encapsulated in the LNP. The present disclosure also provides compositions and methods of making the LNPs and treatment using the same.

A compound or molecular complex. The compound or molecular complex comprises: a metal chelator configured for chelation with a radioactive isotope or a non-radioactive isotope; and a trifluoroborate (BF3)-containing moiety configured for 19F / 18F exchange or a precursor thereof; and optionally a cell-targeting domain.

The invention discloses an E3 ubiquitin enzyme mutant as well as modification and a protein targeted degradation system and application thereof, and particularly relates to a series of targeted protein degradation enhanced E3 ubiquitin enzymes (Trim21-N) and a modification method thereof, the E3 ubiquitin enzymes (Trim21-N) are obtained by modifying a wild type Trim21 (wtTrim21) protein structural domain, and the E3 ubiquitin enzymes comprise Trim21-a, Trim21-b, Trim21-c, Trim21-d, Trim21-e and Trim21-f. The efficiency of degrading the target protein through the ubiquitin proteasome is remarkably improved, and the method has the characteristics of strong endogenous and exogenous universality, high specificity, ubiquitin proteasome dependence, low cytotoxicity, strong cell compatibility and the like on the degradation of the target protein. The invention provides E3 ubiquitin enzyme (Trim21-N) based on a targeted protein degradation enhancement version and an exogenous fluorescence report degradation system of the E3 ubiquitin enzyme (Trim21-N), preferably Trim21-e with the optimal degradation effect, and the E3 ubiquitin enzyme (Trim21-N) is named as delta Trim21. The invention further provides an endogenous protein degradation system based on the delta Trim21. The method has the characteristics of high specificity, rapidness and small module, so that the method can be used for researching various biological and disease mechanisms, including the fields of cell targeted therapy, cell mechanism exploration, genetic engineering and the like.

The present disclosure provides bispecific stealth lipid nanoparticle (LNP) compositions engineered to target specific tissues or cell-types, e.g., hematopoietic stem cells, to modify the cells with therapeutic nucleic acid encapsulated in the LNP. The present disclosure also provides compositions and methods of making the LNPs and treatment using the same.

Methods and compositions for treating fibrosis (e.g., cardiac fibrosis), or other conditions associated with inflammation and / or fibrosis are provided. Methods can include administering a nucleic acid encoding a sialic acid-binding immunoglobulin-type lectin 9 (Siglec-9) protein to a subject in need of fibrosis treatment, where the Siglec-9 protein is expressed by the nucleic acid in regulatory T (Treg) cells in the subject. Methods and compositions can include Treg cells that overexpress Siglec-9 to enhance the ability of Treg cells to target cells expressing amine oxidase, copper containing 3 (AOC3), including fibroblasts or myofibroblasts. In some embodiments, the enhanced Treg cells are targeted to myofibroblasts (e.g., cardiac myofibroblasts) with elevated expression of fibrotic genes.

The invention discloses a specific cell targeted hybrid nano-delivery carrier and a preparation method and application thereof, and aims to solve the problems of insufficient specificity, off-target risk, low delivery efficiency and the like of an existing drug delivery system. And a bionic hybrid nano delivery platform with a natural targeting function and high drug loading capacity is constructed. The vector retains key receptor molecules and signal markers on a source cell membrane, and can actively identify and target corresponding cells; meanwhile, due to the introduction of the lipidosome, the yield and stability of the material are remarkably improved, and the immune clearance rate is reduced. Experimental results show that the nano-carrier shows good targeting and biocompatibility in various disease models, and has wide clinical application prospects in the aspects of tumor treatment, tissue repair, inflammation control, targeted imaging and the like.

The invention belongs to the technical field of biological medicine, and discloses a high-efficiency vascular endothelial cell targeting vesicle system, which is prepared from hemangioma stem cell derived exosome HemSCs-Exos and bone marrow mesenchymal stem cell derived apoptotic small body BMSCs-ABs, and is characterized in that the endothelial cell targeting vesicle system is prepared from the hemangioma stem cell derived exosome HemSCs-Exos and the bone marrow mesenchymal stem cell derived apoptotic small body BMSCs-ABs; meanwhile, the invention further discloses a preparation method of the vesicle system and application of the vesicle system in promoting proliferation and migration of endothelial cells. Different from existing targeting modification, the ingenious targeting relationship between the BMSCs-ABs and the endothelial cells belongs to non-special modification combination, and is simple and efficient; the fusion between the double EVs has the characteristic of realizing '1 + 1gt, 2', not only retains the treatment components of the HemSCs-Exos and the BMSCs-ABs, but also the fused eHEs has remarkable cell specificity distribution, and the fusion mode is simple and stable.

The invention belongs to the technical field of biological medicine and molecular biology, and particularly relates to a single-chain antibody targeting NRP1, a CAR-T cell and application of the single-chain antibody and the CAR-T cell in fibrosis treatment. Four types of high-affinity single-chain antibodies targeting mouse NRP1 antigens are obtained by immunizing mice, the single-chain antibodies are applied to second-generation CAR, T cells of mouse spleen sources are infected after virus packaging, and CAR-T cells are constructed. The CAR-T cells of the targeted NRP1 can be used for effectively killing NRP1 positive cells. In-vivo experiments show that the CAR-T cells can inhibit the growth of NRP1 positive tumor cells. The CAR-T cell can improve the mouse liver fibrosis condition, collagen in the mouse liver is reduced through treatment, and the molecular level of fibrosis markers SMA and NRP1 is reduced, it is indicated that the CAR-T cell recognizes and eliminates activated HSCs through targeting NRP1, and the fibrosis degree is reduced.

Provided are complexes and methods for targeting cells of interest for delivery of a cargo such as an oligomeric compound or an oligomeric duplex. In particular, the complex may comprise a transferrin receptor binding moiety and a half-life extension moiety.

The invention discloses a preparation method of a nuclear magnetic resonance imaging contrast agent based on surface hepatocyte targeting molecule modification ferroferric oxide nanoparticles, which comprises the following steps: synthesizing ferroferric oxide nanoparticles (Fe3O4 NPs) by a thermal decomposition method, and connecting the Fe3O4 NPs with a ligand dopamine-PEG2000-EOB carrying hepatocyte targeting molecules by a ligand exchange method to obtain the nuclear magnetic resonance imaging contrast agent. The nanoparticles Fe3O4-EOB-PEG capable of carrying out selective T2 nuclear magnetic resonance imaging on the hepatocytes are formed. The method is simple and easy to operate, the controllability of the preparation process is high, the biocompatibility of the obtained product is good, T2 signals of hepatocytes can be remarkably improved, the good early diagnosis effect on liver tumors is achieved, and wide application prospects are achieved.

This disclosure relates to VIP antagonist for uses in managing the treatment or prevention of cancer and viral infections. In certain embodiments, this disclosure relates to chimeric variants of VIP antagonists, as peptides disclosed herein, and pharmaceutical composition comprising the same. In certain embodiments, this disclosure contemplates methods of stimulating immune cells to target cancer by mixing immune cells in vitro with peptides disclosed herein and further administering an effective amount of stimulated immune cells to a subject in need of cancer treatment.

The invention discloses an emulsifier for preparing a Pickering emulsion, the Pickering emulsion as well as a preparation method and application of the Pickering emulsion. The emulsifier of the Pickering emulsion is obtained by dissolving distearoyl phosphatidylcholine, cholesterol and distearoyl phosphatidyl ethanolamine-polyethylene glycol 2000 in ethanol, carrying out rotary evaporation to remove ethanol, then adding an antigen aqueous solution containing an antigen, continuing rotary evaporation to obtain liposome nanoparticles, heating the liposome nanoparticles with mannose in a water bath, and carrying out freeze drying. The Pickering emulsion is obtained by dispersing an emulsifier in water as a water phase, taking squalene as an oil phase, mixing the water phase and the oil phase, and homogenizing. The Pickering emulsion disclosed by the invention is prepared by taking antigen presenting cell targeted liposome nanoparticles as a raw material; and the antigen has excellent ion concentration characteristic, pH stability, temperature stability and storage stability, and can protect the integrity of the antigen.

The present invention relates to an isolated cellular targeted delivery system comprising a CD45+ leukocyte cell comprising within said cell a complex of one or more iron binding proteins and / or a label as well as methods for producing such isolated cellular targeted delivery system and uses of such system for therapy diagnosis and in particular for diagnosis of cancer, particularly metastatic cancer, in particular for therapy of cancer.

The invention discloses a prebiotic-loaded intestinal targeting exosome and a preparation method and application thereof.The preparation method comprises the steps that firstly, plasmids containing intestinal cell targeting peptide sequences are constructed through a gene editing technology, the plasmids are transfected and introduced into cells, the transfected cells are screened with antibiotics, and cell strains stably expressing intestinal cell targeting peptides are obtained; then culturing and adding prebiotics, and continuously culturing to enable the cells to take in the prebiotics and release the exosomes loaded with the prebiotics; and finally, collecting cell culture supernate, and centrifuging and resuspending for multiple times under a low-temperature condition to obtain the prebiotics-loaded intestinal targeting exosome. According to the preparation method, extraction of the exosome, loading of the prebiotics and an intestinal targeting modification process are optimized, so that the prepared intestinal targeting exosome loaded with the prebiotics can be used for remarkably improving the loading efficiency and intestinal targeting of the prebiotics and enhancing the stability of the exosome in gastrointestinal tracts; therefore, the delivery efficiency and the treatment effect of the prebiotics in the intestinal tract are improved.

The present disclosure provides combinations of anti-CD19 agents and B cell targeting agents and methods of treating subjects having B cell malignancies with combinations of anti-CD19 agents and a B cell targeting agents.

The application provides an improved hyaluronic acid injection preparation for inflammation targeting and stem cell capture, a preparation method and use thereof, and belongs to the field of medicine. The injection preparation is prepared from unsaturated bond modified hyaluronic acid, stem cell targeting DNA tetrahedron and thiol modified inflammation targeting aptamer as raw materials. The injection preparation can be targeted to accumulate at an osteoarthritis site, capture mesenchymal stem cells in situ, recruit mesenchymal stem cells to the osteoarthritis site, promote differentiation of stem cells into cartilage, promote cartilage repair, play a role in treating osteoarthritis, and has a good application prospect.

The present disclosure provides stealth lipid nanoparticle (LNP) compositions engineered to target specific tissues or cell-types, e.g., T cells, B cells, natural killer cells, to genetically modify the cells with therapeutic nucleic acid encapsulated in the LNP. The present disclosure also provides compositions and methods of making the LNPs and treatment using the same.

The invention discloses lipid nanoparticles targeting liver cells as well as a preparation method and application of the lipid nanoparticles. Raw materials of the lipid nanoparticles comprise lipid targeting dirty cells, and the lipid targeting dirty cells is selected from at least one of galactosyl lipid, N-acetyl galactosamino lipid, lactosyl lipid, mannose-based lipid, glycolipid, glycerol glycolipid, steroid glycolipid, glycerol cholic acid lipid or N-alkenyl lipid. The low-toxicity lipid nanoparticle for efficiently targeting the liver is high in delivery efficiency, has remarkable liver targeting, low immunogenicity and excellent biocompatibility, and is applicable to delivery of various drugs, gene therapy and vaccines needing liver targeting delivery.

A method for determining if an agent is suitable for treating a Rheumatoid Arthritis (RA) patient, the method comprising determining the profile of a first, second and / or third marker panel in a sample from the patient, wherein the agent is selected from an agent that downregulates TNF mediated signalling, an agent that downregulates IL-6 mediated signalling and a B cell targeted therapy.

The invention relates to a therapeutic combination, comprising a first proteinaceous molecule comprising a first binding site for binding to a first epitope of a first cell-surface molecule, the first proteinaceous molecule provided with at least one saponin covalently bound to an amino-acid residue of said first proteinaceous molecule, and comprising a second pharmaceutical composition comprising a second proteinaceous molecule different from the first proteinaceous molecule, the second proteinaceous molecule comprising a second binding site for binding to a second epitope of a second cell-surface molecule different from the first cell-surface molecule, and comprising an effector moiety, wherein the second epitope is different from the first epitope. An aspect of the invention is a composition comprising the first proteinaceous molecule and the second proteinaceous molecule of the invention. The invention also relates to an antibody-drug conjugate comprising the first proteinaceous molecule of the invention and an effector moiety. An aspect of the invention relates to a pharmaceutical composition comprising the composition or the antibody-drug conjugate of the invention, and optionally further comprising a pharmaceutically acceptable excipient. The invention also relates to the therapeutic combination or the composition or the antibody-drug conjugate or the pharmaceutical composition of the invention, for use as a medicament. The invention also relates to the therapeutic combination of the invention for use in the treatment or prophylaxis of a cancer.

The present disclosure provides methods and compositions for modulating cell surface proteins and receptor complexes using a novel class of glycan conjugates that can be used to engage the signaling pathways within desired c cell types. Such defined cell-targeting bioactive glyco-ligands are directed for cell engagement and activation in therapeutic applications.

The invention provides a cell-targeted drug preliminary screening model training method, a drug preliminary screening method and equipment, and the method comprises the steps: obtaining molecular fingerprint feature data corresponding to each compound sample with label information to form a corresponding original data set, and carrying out the data screening of the original data set in a distance measurement mode, and training a regression model based on a graph neural network to learn the structural topology of each compound sample, and training the model as a cell-targeted drug preliminary screening model for predicting whether the compound has potential cell-targeted drug activity or not. According to the application, the comprehensiveness of molecular characterization can be effectively improved in the training process of the cell-targeted drug preliminary screening model, and the generalization ability of the trained cell-targeted drug preliminary screening model can be effectively improved, so that the application universality of the trained cell-targeted drug preliminary screening model can be effectively improved; and the accuracy and the reliability of a potential cell targeted drug activity prediction result predicted by the model can be improved.

Nanoparticles for engineering cells to express target antigens and methods of treating / preventing cancer or solid tumors using the same.

The invention discloses mucosal immune-enhanced recombinant lactobacillus for expressing PEDV (porcine epidemic diarrhea virus) S1 protein as well as a construction method and application of the mucosal immune-enhanced recombinant lactobacillus. The mucosal immune-enhanced recombinant lactobacillus contains a recombinant lactobacillus expression vector for expressing PEDV S1 protein, the amino acid of the PEDV S1 protein is fused with M cell targeting peptide (Co1) and dendritic cell targeting peptide (6aa), the carboxyl terminal of the PEDV S1 protein is fused with a mucosal immune adjuvant (LTB), and the connection sequence of all the parts is Co1-6aa-S1-LTB. According to the mucosal immune enhanced recombinant lactobacillus constructed by the invention, through the synergistic effect of the targeting peptide (DC / MC targeting peptide) and the adjuvant (LTB), the mucosal immune response efficiency (including intestinal mucus SIgA and serum IgG levels) of a PEDV S1 antigen is remarkably improved, humoral immunity, cellular immunity and mucosal immune responses of pregnant animals can be remarkably induced, maternal antibodies are generated, and the immune response efficiency of the pregnant animals is remarkably improved. The intestinal SIgA level of newborn animals is improved, and an effective technical means is provided for prevention and treatment of PED.

The application relates to a T cell-targeting nanoparticle based on a nucleic acid aptamer and a preparation method and application thereof, in particular to a T cell-targeting lipid aptamer, wherein the lipid aptamer comprises a hydrophobic molecule and a nucleic acid aptamer, the nucleic acid aptamer comprises at least one nucleic acid aptamer for targeting a T cell surface molecule, and the molar ratio of the hydrophobic molecule and the nucleic acid aptamer is 5000:1-1:10. The lipid aptamer or the nanoparticle formed by self-assembly technology of the lipid aptamer can realize cell 'pointing' gene modification and in-vivo gene reprogramming of cells.

The invention relates to a CAR-T (Chimeric Antigen Receptor-T) cell targeting SLC7A11.

The invention belongs to the technical field of biological medicines, and discloses a B cell and cartilage cell senescence targeting osteoarthritis treatment medicine. The invention provides an application of an anti-MIF antibody or an antigen binding fragment thereof as a B cell targeting immunomodulator in osteoarthritis treatment drugs, the anti-MIF antibody or the antigen binding fragment thereof regulates and controls an MIF / HMGB1 / MMP13 signal axis through a neutralization effect with MIF, so that the MIF and B cells are significantly co-localized, expression of HMGB1 in the B cells is promoted, and the osteoarthritis treatment effect is improved. The senescence of B cells is reduced and the B cells are promoted to regulate or repair phenotype transformation so as to destroy chronic inflammatory circulation and diffusion of pathogenic plasma cells, and the expression of MMP13 in joint tissues is reduced so as to maintain the steady state of cartilage tissues; the preparation method has an excellent application prospect in preparation of an OA intra-articular injection drug which realizes rapid anti-inflammatory and long-term cartilage protection effects and can realize a lasting curative effect through low-frequency drug delivery.

The invention discloses a regulation mechanism research method of depleted precursor CD8T cells, and relates to the field of immunology and molecular biology. Comprising the following steps: detecting the expression level of the ARHGAP9 gene in a chronic virus infection model; constructing a T cell specific ARHGAP9 gene knockout animal model; the influence of ARHGAP9 deletion on the frequency, phenotype and function of the Tpex cell is analyzed; a single cell transcriptome sequencing technology reveals that ARHGAP9 regulates and controls a downstream signal channel of a Tpex cell. By constructing a chronic virus infection model, detecting the expression dynamic state of the ARHGAP9 gene, knocking out an animal model by utilizing T cell specificity ARHGAP9, and combining flow cytometry, qPCR, single cell transcriptome sequencing and other technologies, the invention discloses the effect of the ARHGAP9 as a novel immune checkpoint molecule, and provides a theoretical basis for developing Tpex cell targeting immunotherapy.