28 results about "Cell selectivity" patented technology

The invention discloses a full D-type antibacterial peptide with high enzymolysis stability and broad-spectrum antibacterial activity and application thereof. The antibacterial peptide is obtained by sequentially and repeatedly arranging D-type tryptophan, D-type arginine and D-type lysine for four times and carrying out C-terminal amidation; the amino acid sequence of the gene is (D-Trp)-(D-Arg)-(D-Lys)-(D-Trp)-(D-Arg)-(D-Lys)-(D-Trp)-(D-Arg)-(D-Lys)-(D-Trp)-(D-Arg)-(D-Lys)-(D-Trp)-(D-Arg)-(D-Lys)-NH2, and is marked as DWRK-12. The antibacterial peptide shows broad-spectrum antibacterial activity and excellent stability, can effectively resist clinically separated multidrug resistant strains, and keeps high cell selectivity at the same time. Due to the characteristics, the antibacterial peptide has important application value in the aspect of developing novel antibacterial drugs, especially in the field of treatment of infection of multiple drug-resistant bacteria.

The invention provides a duodenal mucosa adjusting system and method based on pulsed electric field ablation and application of the duodenal mucosa adjusting system and method in diabetes treatment, the duodenal mucosa adjusting system comprises an intelligent control host capable of achieving bidirectional data transmission and an adjustable catheter, and the intelligent control host initializes parameters and adjusts pulse parameters by monitoring impedance data in real time until pulses are interrupted or terminated; periodic ablation is carried out, periodic intervals are used for measuring impedance data, the ablation depth is evaluated according to the impedance change rate, and whether next section ablation is carried out or not is judged till full-area ablation is completed. The far-end ablation adopts a structure of combining fusiform flexible support and annular electrode spiral arrangement to ensure that an ablation field uniformly covers mucous membrane plica of a duodenum bulb part and a descending part; a cell selective ablation mechanism is adopted, the critical electric field intensity is set, K cell electroporation is selectively induced, and meanwhile goblet cells are protected.

Disclosed are compositions and methods useful for targeting and internalizing molecules into cells of interest and for penetration by molecules of tissues of interest. The compositions and methods are based on peptide sequences that are selectively internalized by a cell, penetrate tissue, or both. The disclosed internalization and tissue penetration is useful for delivering therapeutic and detectable agents to cells and tissues of interest.

The invention relates to the combination of a cell-selective promoter to drive the N-terminal part of the transgene and a compact ubiquitous promoter with similar expression levels to drive the C-terminal part of the transgene (or vice versa) for dual AAV intein-mediated delivery to obtain cell-selective, efficient transgene expression.

Programmable guide RNAs (gRNAs) play a central role in the CRISPR revolution sweeping biology and medicine by directing the function of a Cas protein effector to a target gene of choice. To achieve programmable control over regulatory scope, the activity of a conditional guide RNA (cgRNA) depends on the presence or absence of an RNA trigger, allowing for cell-selective regulation of CRISPR / Cas function. Unlike a standard gRNA, a cgRNA is programmable at multiple levels, with the target-binding sequence controlling the target of Cas activity (edit, silence, induce, or bind a gene of choice) and the triggerbinding sequence controlling the scope of Cas activity. cgRNA mechanisms that are allosteric allow for independent design of the target and trigger sequences, providing the flexibility to select the regulatory target and scope independently. Disclosed herein are allosteric cgRNA mechanisms for both ON→OFF logic (conditional inactivation by an RNA trigger) and OFF→ON logic (conditional activation by an RNA trigger). Allosteric cgRNAs enable restriction of CRISPR / Cas function to a desired cell type, tissue, organ, or disease state. Allosteric cgRNAs provide a versatile platform for cell-selective and tissue-selective research tools, biotechnologies, diagnostics, and therapeutics.

The invention discloses a cell-penetrating peptide CPP137 as well as a compound, a composition and application thereof, and belongs to the technical field of polypeptides. According to the application, a cell-penetrating peptide CPP137 with immune cell selectivity is screened out from a plague bacillus sORF library. The polypeptide not only can be efficiently internalized by THP-1 (M0 type) mononuclear cells, but also can specifically target two key antigen presenting cells, namely primary macrophages and dendritic cells (DC), in a complex human whole blood physiological environment, but is not obviously combined with other blood cell types. Therefore, the cell-penetrating peptide CPP137 is a targeted delivery carrier with great potential, can be used for specifically delivering a therapeutic load to myeloid immune cells, and is used for treating intracellular infection and immune-related diseases or used as a vaccine development platform. Meanwhile, CPP137 can also be used as a specific diagnostic marker or an imaging probe for detecting or tracing pathological states related to macrophages / DC.

This invention discloses a type of click-type covalent drug, its regionally selective delivery system, and its applications. The invention comprises two parts: a click-type covalent drug and a tumor regionally selective delivery system. The click-type covalent drug consists of three parts: an azacyclic alkyne (DBCO), a small molecule drug, and a linker, having the structure of Formula 1. Optionally, the small molecule drug is a membrane protein inhibitor, an immunomodulator, or a chemotherapeutic drug. The click-type covalent drug reacts with azide-labeled target cells via a click reaction, forming a covalent bond that binds to the cell membrane, increasing the local drug concentration and prolonging the drug retention time, thereby enhancing selective inhibition of the target cells. The regionally selective delivery system is co-assembled from an amphiphilic block polymer and the click-type covalent drug for regionally selective delivery. This invention achieves covalent binding to azide-labeled tumor cells through the click-type covalent drug, while having no effect on unlabeled normal cells, reducing toxic side effects on normal tissues.

The disclosure features compositions or systems and uses thereof, comprising a first polynucleotide encoding a target molecule, optionally a second polynucleotide encoding an effector, repressor, or endonuclease molecule; optionally a recognition or cleavage site in the first or second polynucleotide, and optionally a repressor / effector binding site in the first polynucleotide. The disclosure also features compositions or systems and uses thereof, comprising a messenger RNA (mRNA) comprising (i) an open reading frame encoding a polypeptide, and (ii) at least six miR142 target sites.

This invention belongs to the field of guided bone regeneration materials technology, specifically relating to an arginine carbon dot photoinitiated hydrogel prepolymer, its preparation method, and its application. The arginine carbon dot photoinitiated hydrogel prepolymer of this invention, when used for alveolar bone regeneration, inhibits the proliferation / migration of gingival fibroblasts (hGFs) while simultaneously inducing and promoting the proliferation / migration and osteogenic differentiation of bone marrow mesenchymal stem cells (hBMSCs), thus creating a "reverse-response" cell-selective regulatory effect.

The present disclosure provides compositions and methods for the selective transduction and genome editing of human cells (e.g., hematopoietic stem and progenitors cells, HSPCs) using engineered viral like particles (eVLPs). Aspects of the disclosure provide eVLP compositions comprising fusion proteins comprising a targeting moiety. In some embodiments, the fusion proteins comprise a cytokine conjugated to a transmembrane protein and / or an envelope glycoprotein. In other embodiments, the fusion proteins comprise a targeting moiety domain, a stalk protein domain, a transmembrane and / or envelope glycoprotein domain. Targeted-eVLP architectures comprising various targeting domains, stalk domains, transmembrane domains, and envelope glycoproteins are also provided herein. Other aspects of the disclosure provide eVLP compositions comprising envelope glycoproteins comprising non-natural sugars and methods of conjugating said eVLPs to various targeting moieties using bio-orthogonal click chemistry. Polynucleotides, vectors, cells, and kits useful for producing the articles, and performing the methods, described herein are also provided.

The invention discloses a lipidosome drug delivery system, a preparation method thereof, a lipidosome preparation, application, and a fat-reducing drug or a medical beauty product containing the lipidosome drug delivery system. The liposome drug delivery system comprises deoxycholic acid and phospholipid; the phospholipids comprise a first phospholipid and optionally comprise a second phospholipid; the mass ratio of deoxycholic acid to phospholipid is (1: 2.5)-(1: 35). The drug delivery system can be further prepared into a liposome preparation which is used for fat-reducing drugs or medical beauty supplies. The lipidosome drug delivery system, the lipidosome preparation drug or the medical beauty product has excellent adipocyte selectivity, realizes a good adipose tissue dissolving effect, has small side effects and high safety, and has a good market application prospect.

The invention provides a preparation method and application of a tumor targeting peptide / cell penetrating peptide-SN38 conjugate, and belongs to the technical field of polypeptide preparation and biological medicine. The invention provides a series of novel tumor targeting peptide / cell penetrating peptide-SN38 conjugates, and provides an efficient synthesis method of polypeptide solid phase coupling SN38. The novel tumor targeting peptide / cell penetrating peptide-SN38 conjugate prepared by the invention can effectively solve a series of defects of poor cell selectivity, poor water solubility, poor uptake and the like of SN38, shows a relatively strong effect of inhibiting tumor cell proliferation, further improves the anti-tumor application potential of SN38, and realizes a safer and more effective cancer treatment function.

The application discloses a deer-derived antibacterial peptide against gram-negative bacteria and a preparation method and application thereof, belongs to the technical field of biology, and the amino acid sequence is shown as SEQ ID No. 1. It is tested that the antibacterial peptide S6 has obvious inhibiting effect on most of tested gram-negative bacteria, the average antibacterial activity reaches 8.00 muM, the hemolytic activity and cytotoxicity are relatively low, the cell selectivity index is 32, and the antibacterial peptide S6 has relatively strong anti-enzymatic ability. The antibacterial mechanism of the antibacterial peptide S6 is determined, it is judged that the antibacterial peptide S6 has recognition and damage effects on the cell membrane of gram-negative bacteria, and finally leads to the death of bacteria. Therefore, the antibacterial peptide S6 is an antibacterial peptide against gram-negative bacteria with high clinical application value.

The invention provides a microbial production cell for the synthesis of a product, further comprising a charge-dependent genetic circuit whose expression confers a selective growth and / or survival advantage to those cells that synthesize the product, while limiting the proliferation of unproductive or non-productive escape cells.

The present application relates to the technical field of submicron preparation of organic active ingredients, and discloses a nerve immunoregulator targeting microglia cells and a preparation method thereof, which comprises the following steps: mixing a parasite kinase inhibitor and a lipid carrier material in anhydrous ethanol to configure a clear and uniform phase mixed mother liquor, dropping the mixed mother liquor into deionized water, and dispersing and wrapping the mixed mother liquor in a continuous ultrasonic field to form a preparation suspension containing drug lipid microparticles; centrifugally separating the preparation suspension containing drug lipid microparticles to collect precipitates; resuspending the precipitates in a mannitol aqueous solution; and removing water by vacuum freeze-drying. The present application regulates the crystallization kinetics path, inhibits spontaneous aggregation of the raw drug to guarantee the spatial stability of the preparation, improves the selective enrichment degree of central target cells, crosses the barrier along the pathological leakage channel, and releases the active ingredients in situ to calm the neuroimmunological storm.

A minimally invasive penetrating microelectrode array is used to generate localized electric field “hotspots” for delivering biomolecules, such as nucleic acid or protein molecules, into cells located in the epidermal or dermal layer of the skin via transient membrane permeabilization. The “hotspots” can be controlled by selectively insulating the penetrating microelectrodes at specific regions. The portion of microelectrodes that are not covered with insulation coating can be coated with nucleic acid or protein vaccine vector, or other biomolecules to be delivered. Upon insertion into the skin, an anchor microelectrode region mechanically anchors the penetrating microelectrode to position the target tissue microelectrode region, so as to selectively align the biomolecule coating with cells located in the tissue location. The biomolecule coating will dissolve when in contact with surrounding tissue. By applying an electrical pulse, the biomolecules can be delivered into surrounding cells.

The invention relates to the technical field of medicinal chemistry, and particularly discloses a 2, 7-naphthyridine-1-ketone derivative as well as a preparation method and application thereof. The 2, 7-naphthyridine-1-ketone inhibitor is directionally designed and synthesized by focusing on an ATP binding pocket of HPK1 enzyme and analyzing hydrogen bond donor / receptor sites and hydrophobic interaction sites in the region. The 2, 7-naphthyridine-1-ketone derivative is novel in structure, has good HPK1 inhibition activity, shows an excellent inhibition effect on various tumor cells of a human body in a cellular level experiment, and has broad-spectrum and efficient anti-tumor characteristics. Meanwhile, the compound shows good cell selectivity when exerting pharmacological activity, has a weak inhibition effect on normal cells on the premise of effectively inhibiting tumor cell proliferation, can significantly reduce the risk of damage of drugs to normal tissues of a human body, improves the medication safety, and lays an important foundation for clinical treatment of tumors.

The invention discloses an antibacterial peptide, a preparation method and application of the antibacterial peptide in preventing and treating oral problems, and belongs to the technical field of antibacterial peptides. The amino acid sequence of the antibacterial peptide is FIRLLKSAGKAIHKLIRRGH, and the amino acid sequence of the antibacterial peptide is shown in the description. In-vitro experiments show that the compound has broad-spectrum antibacterial activity on oral pathogens such as fusobacterium nucleatum, porphyromonas gingivalis and streptococcus mutans, the minimum inhibitory concentration is 31.25-125 mu g / mL, no obvious hemolysis effect exists, the therapeutic index reaches 50.79, the cell selectivity is high, and certain protection and anti-inflammatory effects are achieved in a Pg-induced human gingival fibroblast in-vitro inflammatory model. The traditional Chinese medicine composition has a certain potential effect of inhibiting oral gingivitis. The invention provides an important research and development thought for the development of novel oral disease treatment medicines and nursing products, and has a good application prospect.

The application provides a D-pi-A type organic antibacterial photosensitizer and a synthesis method and application thereof, and belongs to the field of photosensitizers and antibacterial photodynamic therapy; the application takes methoxy-substituted triphenylamine as an electron donor, pyridine salt as an electron acceptor, and thiophene as an electron pi bridge; through a series of simple organic reactions, an AIE type photosensitizer with bacterial cell selectivity is synthesized, and the photosensitizer can be applied to antibacterial photodynamic therapy; the photosensitizer can realize bacterial imaging and selectively exert photodynamic effect on bacteria by connecting a hydrophilic group, has good therapeutic effect and biological safety, and has strong application prospect in antibacterial photodynamic therapy.

The invention provides a microbial production cell for the synthesis of a product, further comprising a genetic charge addition circuit whose expression confers a selective growth and / or survival advantage to those cells that synthesize the product; while limiting the proliferation of unproductive or non-productive escape cells.

The invention relates to the technical field of bioengineering and nucleic acid regulation and control, discloses a relational nucleic acid circuit design scheme based on an interaction relationship between nucleic acid and an expression product, and aims to solve the problems that an existing nucleic acid regulation and control tool lacks cell selectivity and nucleic acid circuit elements are complex. The scheme comprises the following steps: acquiring nucleic acid information of target and non-target cells; screening specific nucleic acid of a target cell, and combing the interaction relationship of nucleic acid covering DNA, RNA, protein and a special regulation layer and an expression product of the nucleic acid; a modular nucleic acid circuit containing D-type sensor nucleic acid, A-type regulation and control nucleic acid and B-type effect nucleic acid is constructed, and only when all the D-type nucleic acid recognizes specific nucleic acid, the B-type nucleic acid transmits regulation and control signals step by step and expresses the regulation and control signals; and an adaptive vector is selected and introduced into a target cell to realize accurate intervention. The invention has the advantages of strong targeting property and simplified elements, can adapt to various scenes such as tumor cells, pathological cells, normal target cells and the like, and provides a general scheme for precise cell intervention.

This invention discloses a vascular graft that maintains the contractile phenotype of smooth muscle cells and its preparation method. The vascular graft is modified with a polydopamine coating on its luminal surface, anchoring RGD / CD47 dual-modified lipid nanoparticles, which encapsulate mRNA encoding olarumab. After implantation, the dual-modified LNPs specifically target endothelial cells, achieving highly efficient transfection and enabling endothelial cells to continuously secrete olarumab in situ, thereby blocking the PDGF-BB / PDGFR-α signaling pathway, maintaining the contractile phenotype of smooth muscle cells, and significantly inhibiting restenosis and calcification of the vascular graft. Experiments show that the dual-modified LNPs have a transfection efficiency of >90% in endothelial cells, exhibiting an unexpected synergistic effect of cell-selective delivery.

The invention discloses a gram-negative bacterium resisting deer derived antibacterial peptide as well as a preparation method and application thereof, and belongs to the technical field of biology, the amino acid sequence of the antibacterial peptide is as shown in SEQ ID No.1, tests show that the antibacterial peptide S6 has an obvious inhibition effect on most of tested gram-negative bacteria, the average antibacterial activity reaches 8.00 mu M, the hemolytic activity and cytotoxicity are relatively low, and the antibacterial peptide S6 can be applied to preparation of anti-gram-negative bacterium anti-deer derived antibacterial peptide. The cell selectivity index is 32, and meanwhile, the high enzymolysis resistance is achieved; the antibacterial mechanism of the antibacterial peptide S6 is measured, and it is judged that the antibacterial peptide S6 has recognition and destruction effects on cell membranes of gram-negative bacteria and finally causes bacterial death; therefore, the antibacterial peptide S6 disclosed by the invention is a gram-negative bacterium resistant antibacterial peptide with high clinical application value.

Provided is a new amino acid derivative. The amino acid derivative can be selectively incorporated into LAT1-expressing cells.　The present invention relates to a compound represented by formula (I) or a pharmaceutically acceptable salt thereof: In formula (I), ring A represents a ring structure; R1 independently represent various groups; -X- represents a linking group; -Y- represents an arbitrary ring, an alkynyl, or a bond; -Z- represents –(CR17R18)m-, R2 represents hydrogen, a substituted or unsubstituted alkyl, a substituted or unsubstituted alkyloxy, or a substituted or unsubstituted amino; R3 represents a group having a chain structure represented by -B(NR300)2 or -B(OR300)2, or, together with atom B, a group having a cyclic structure of R30R40, for example, a group represented by -BR30R40.

This invention discloses an autophagy regulator, its preparation method, and its applications, aiming to solve the problems of single-target autophagy regulation, lack of cell selectivity, and poor efficacy in killing cancer cells in existing technologies. The autophagy regulator has the following structural formula: [structural formula would be inserted here]. This autophagy regulator can simultaneously target mitochondria and lysosomes, inducing mitophagy; it can also disrupt lysosomes, inhibiting autophagic flux; it can be used for mitochondrial and lysosomal imaging, and can also be used as an anticancer drug.

This invention discloses a biomimetic hybrid liposome nanomedicine co-loaded with senolytic drugs and antibiotics, its preparation method, and its applications. The nanomedicine uses egg yolk lecithin and cholesterol as lipid materials. The Bcl-2 / Bcl-xL inhibitor ABT-263 is loaded into a lipid bilayer, and the antibiotic ciprofloxacin hydrochloride is encapsulated in an aqueous core. After preparing co-loaded liposomes using a thin-film hydration-ultrasound-extrusion-ultrafiltration method, the liposomes are fused with doxorubicin-induced senescent tumor cell membranes via ultrasound-assisted physical extrusion. The resulting biomimetic hybrid liposome possesses multiple functions, including homologous targeting of senescent tumor cells, selective removal of senescent cells, and killing of senescent bacteria. Combined use with 5-fluorouracil can enhance the killing effect on senescent tumor cells. This invention belongs to the field of biomedical nanotechnology.

This invention relates to a three-dimensional scaffold based on chirality and peptides for selective cell adhesion, its preparation method, and its applications, relating to the field of medical products. The three-dimensional scaffold is a stacked, three-dimensional ordered structure, with each layer comprising several ordered polyelectrolyte multilayer membrane soft carriers arranged at an angle between adjacent layers. Each layer of the polyelectrolyte multilayer membrane is formed by alternating deposition of positively charged chiral molecules grafted with specific recognition groups and negatively charged supramolecular polyelectrolytes on the soft carriers, followed by modification with peptides. The two peptides in adjacent polyelectrolyte multilayer membranes are different and are used to promote the specific adhesion of different cells. The three-dimensional scaffold provided by this invention has specific adhesion properties, thereby avoiding excessive cell proliferation in incorrect locations and helping to prevent problems such as re-injury and stenosis of artificial blood vessels.

An operational unit for locating and neutralizing pathogen cells in blood includes a time use cassette which has a plurality of thin holding chambers that are filled with blood drawn from a patient. A light source illuminates each of the holding chambers and passes light to an underlying sensor array such that the cells in the blood selectively block the light to produce shadow images of the cells in the sensor array. A processor performs pattern recognition to identify and locate the pathogen cells by use of an image library. After the pathogen cells are located, an electric field is activated in the cassette chamber areas that include the identified pathogen cells. Sufficient electric field energy is applied to destroy the identified pathogen cells. A pump refills the cassette holding chambers, returns the neutralized-pathogen blood to the patient, and the process is repeated for a period of time.