8results about How to "Avoid off-target effects" patented technology

The invention belongs to the field of biological medicines, and relates to a drug-loaded nano-vesicle as well as a preparation method and application thereof. The drug-loaded nano-vesicle comprises a vesicle core and a drug-loaded nano-vesicle, wherein the vesicle core comprises siRNA (small interfering Ribonucleic Acid) capable of specifically targeting and silencing an NR1D1 gene; the vesicle membrane is formed by fusing an erythrocyte membrane, a macrophage membrane, cardiolipin, cholesterol and lecithin. The drug-loaded nano-vesicle can specifically target macrophages in a sepsis immunosuppression stage, has an intracellular response release function, recovers BMAL1 and IGF2BP2-ATP6V1B2 / ATP6V0c axis functions by inhibiting NR1D1 expression, reconstructs a macrophage phagocytosis function and lysosome-dependent bacterium removal capability, and can be used for preparing a drug-loaded nano-vesicle with a specific targeting function. The survival rate of sepsis immunosuppression model animals is obviously improved; and the bacterial load is reduced. Compared with a traditional electroporation method, the preparation method disclosed by the invention has the advantage that the encapsulation efficiency of siRNA is remarkably improved.

On one hand, the invention discloses an anti-FOLR1 single-domain antibody VHH-F01, the amino acid sequence of the VHH-F01 is as shown in SEQ ID NO: 2, and the gene sequence of the VHH-F01 is as shown in SEQ ID NO: 1. The invention also discloses an umbilical cord mesenchymal stem cell preparation, which is characterized in that the preparation introduces the single-domain antibody VHH-F01 targeting the human FOLR1 and the gene of the human Bcl-2 anti-apoptotic protein into umbilical cord mesenchymal stem cells together through a lentiviral vector to obtain a stable and high-expression cell population; vHH-F01 expressed on the membrane surface of the preparation can specifically recognize ovarian cancer cells highly expressed by FOLR1 and can be combined with the ovarian cancer cells highly expressed by FOLR1 with high affinity, and meanwhile, the survival ability of stem cells in a tumor microenvironment can be remarkably enhanced by intracellular highly expressed Bcl-2 protein. In-vitro and animal experiments show that the preparation has excellent targeting homing efficiency and remarkable tumor inhibition effect on ovarian cancer tissues, can effectively prolong the lifetime of model animals, and provides a novel efficient targeting treatment tool for cell therapy of ovarian cancer.

The invention discloses artificial saliva and a preparation method of artificial saliva hydrogel. The artificial saliva is prepared from the following raw materials in parts by mass: 0.5 to 1 g of KCl, 0.2 to 0.4 g of K2HPO4, 0.2 to 0.8 g of NaCl, 0.2 to 0.4 g of KH2P O4, 10.04 to 20.8 g of CaCl2, 1.5 to 3 g of Nacaboxymethlecellulose, 60 to 120 mg of brown moss alcohol, 495 to 1000 ml of natural coconut juice and 5 to 10 ml of herba sarcandrae extract. By selecting the glabrous sarcandra herb extract, anti-inflammatory and anti-tumor treatment is realized, so that the traditional Chinese medicine composition has a remarkable effect on dry mouth caused by radiotherapy; through the form of a gel bead preparation, the beverage is more portable and unique in taste. The gel beads serve as one of oral local administration preparations, and after the gel beads are exploded, drugs can target small glands which are located below oral mucosa and secrete saliva, and the rapid drug effect is achieved. Direct local administration to the oral mucosa may provide rapid drug action, activate small salivary glands within the buccal mucosa, while avoiding systemic drug exposure and off-target effect.

The invention provides mannosylated beta-lactoglobulin-curcumin nanoparticles as well as a preparation method and application thereof, and belongs to the technical field of medicines. The preparation method provided by the invention comprises the following steps: mixing a mannose solution and a beta-lactoglobulin solution, and sequentially carrying out first reaction, dialysis and freeze drying to obtain a mannosylated beta-lactoglobulin monomer; the preparation method comprises the following steps: dissolving mannosylated beta-lactoglobulin in water to obtain a mannosylated beta-lactoglobulin monomer solution, then mixing the mannosylated beta-lactoglobulin monomer solution with a first curcumin-ethanol solution, then adjusting the pH value, then sequentially carrying out incubation and a second reaction to obtain a mannosylated beta-lactoglobulin-curcumin compound, then carrying out a third reaction on the mannosylated beta-lactoglobulin-curcumin compound and a second curcumin-ethanol solution to obtain the mannosylated beta- and finally, dissolving the mannosylated beta-lactoglobulin-curcumin primary nano-particles in an MES buffer solution, adding absolute ethyl alcohol, and carrying out a fourth reaction, so as to obtain the mannosylated beta-lactoglobulin-curcumin secondary nano-particles.

This invention discloses a viral vector targeting KIF4A to inhibit angiogenesis, its preparation method, and its applications. The viral vector contains three shRNA gene fragments targeting the KIF4 protein-coding region, as shown in SEQ ID NO.1-SEQ ID NO.3. Using a lentiviral packaging system, a stable KIF4A knockdown cell line can be constructed, effectively inhibiting endothelial cell proliferation and angiogenesis, and also inhibiting the paracrine promotion of angiogenesis by glioma cells, providing a new strategy for selecting targets for anti-angiogenic tumor therapy.

The invention belongs to the technical field of gene engineering, and discloses a plasmid targeting a ZDHHC5 gene in order to solve the problems of transient effect, low knock-down efficiency and high off-target rate of the existing siRNA technology. The plasmid comprises a DNA sequence for expressing shRNA, preferably a SEQ ID NO: 1 site, adopts a stem-loop structure 'CTCGAG' to improve stability, and integrates green fluorescent protein and puromycin resistance genes on the basis of a lentiviral vector to realize visual screening and long-term expression after transfection. And by optimizing the shRNA design and the special transfection process, the specificity and repeatability are remarkably enhanced. Experiments show that the plasmid can efficiently inhibit ZDHHC5 expression, effectively inhibit proliferation in Huh-7 cells and induce apoptosis.

The invention relates to application of a tomato leaf miner neuropeptide Tachynin gene in regulation and control of embryonic development of tomato leaf miners and prevention and control of tomato leaf miners. The invention relates to the field of biological prevention and control of agricultural pests, in particular to application of a tomato leaf miner neuropeptide Tachykinin gene to regulation and control of the reproductive function of tomato leaf miners and prevention and control of tomato leaf miners. The selected Tachkinin gene of the tomato leaf miner is a key gene for reproductive regulation of the tomato leaf miner, and the knockout of the Tachkinin gene can directly lead to the blocking of embryonic development of the tomato leaf miner.

The invention relates to the field of biological prevention and control of agricultural pests, in particular to application of a tomato leaf miner neuropeptide NTL gene to regulation and control of the reproductive function of tomato leaf miners and prevention and control of tomato leaf miners. The selected tomato leaf miner NTL gene is a key gene for reproductive regulation, NTL gene knockout can directly cause reproductive function disorder of tomato leaf miner, single female egg laying amount and egg hatching rate to be greatly reduced, field population density can be rapidly reduced in combination with a population release technology, and the prevention and treatment effect is superior to that of a traditional chemical pesticide.