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140 results about "Cell penetration" patented technology

Development of Protein-Based Biotherapeutics That Penetrates Cell-Membrane and Induces Anti-Hepatocellular Carcinoma Effect - Improved Cell-Permeable Suppressor of Cytokine Signaling (iCP-SOCS3) Proteins, Polynucleotides Encoding the Same, and Anti-Hepatocellular Carcinoma Compositions Comprising the Same

Protein transduction exploits the ability of some cell-penetrating peptide (CPP) sequences to enhance the uptake of proteins and other macromolecules by mammalian cells. Previously developed hydrophobic CPPs, named membrane translocating sequence (MTS), membrane translocating motif (MTM) and macromolecule transduction domain (MTD), are able to deliver biologically active proteins into a variety of cells and tissues. Various cargo proteins fused to these CPPs have been used to test the functional and/or therapeutic efficacy of protein transduction. For example, recombinant proteins consisting of suppressor of cytokine signaling 3 protein (CP-SOCS3) fused to the fibroblast growth factor (FGF) 4-derived MTM were developed to inhibit inflammation and apoptosis. However, CP-SOCS3 fusion proteins expressed in bacteria were hard to purify in soluble form. To address these critical limitations, CPP sequences called advanced MTDs (aMTD) have been developed in this art. This is accomplished by (i) analyzing previous developed hydrophobic CPP sequences to identify specific critical factors (CFs) that affect intracellular delivery potential and (ii) constructing artificial aMTD sequences satisfied for each critical factor. In addition, solubilization domains (SDs) have been incorporated into the aMTD-fused SOCS3 recombinant proteins to enhance solubility with corresponding increases in protein yield and cell-/tissue-permeability. These recombinant SOCS3 proteins fused to aMTD/SD having much higher solubility/yield and cell-/tissue-permeability have been named as improved cell-permeable SOCS3 (iCP-SOCS3) proteins. Previously developed CP-SOCS3 proteins fused to MTM were only tested or used as anti-inflammatory agents to treat acute liver injury. In the present art, iCP-SOCS3 proteins have been tested for use as anti-cancer agents in the treatment of hepatocellular carcinoma. Since SOCS3 is frequently deleted in and loss of SOCS3 in hepatocytes promotes resistance to apoptosis and proliferation, we reasoned that iCP-SOCS3 could be used as a protein-based intracellular replacement therapy for the treatment of hepatocellular carcinoma. The results support this reasoning: treatment of hepatocellular carcinoma cells with iCP-SOCS3 results in reduced cancer cell viability, enhanced apoptosis and loss of cell migration/invasion potential. Furthermore, iCP-SOCS3 inhibits the growth of hepatocellular carcinoma in a subcutaneous xenografts model. In the present invention with iCP-SOCS3 fused to an empirically determined combination of newly developed aMTD and customized SD, macromolecule intracellular transduction technology (MITT) enabled by the advanced MTD may provide novel protein therapy against hepatocellular carcinoma.
Owner:CELLIVERY THERAPEUTICS

Stapled-RGD polypeptide, and applications thereof in tumor targeting delivery

The invention belongs to the field of pharmacology, and relates to stapled-RGD polypeptide, and applications thereof in tumor targeting delivery. Multifunctional targeting polypeptide molecule stapled-RGD with high combination activity with integrin and biological membrane barrier penetration capacity is designed and prepared based on binding peptide cyclization technology; and preparation of fluorescein, drugs, and high molecule carriers modified by the multifunctional targeting polypeptide molecule stapled-RGD, and applications of the fluorescein, the drugs, and the high molecule carriers in tumor imaging and construction of targeted therapy targeted drug delivery systems are disclosed. It is shown by results that specific uptaking of model drugs carried by stapled-RGD by positive cells, tumor mimicry vessels, and tumor ball tissues of expressed integrin is realized, higher tumor targeting capacity, imaging functions, and membrane barrier cell penetration capacity are achieved; nano targeted drug delivery systems constructed by the high molecule carriers modified by stapled-RGD can be used for delivering carried model drugs to target tissues, antitumor drug effect is improved obviously; and stapled-RGD possesses a promising application prospect in mediating drugs, nano targeted drug delivery system membrane barrier penetration, active target searching, tumor diagnosis, and targeted therapy.
Owner:FUDAN UNIV

Full-automatic determining instrument of red blood cell osmotic fragility

The invention discloses a full-automatic determining instrument of red blood cell osmotic fragility. The full-automatic determining instrument is based on the principle of light-proof turbidimetry and consists of a sample absorbing device, an automatic electromechanical device, a light detector and a circuit system, wherein the sample absorbing device is used for absorbing a blood sample through the instrument; the automatic electromechanical device is used for accomplishing various control actions in the automatic measurement of the instrument; the light detector is used for radiating reaction liquid to generate a permeable light signal; the circuit system is used for controlling various stepper motors, electromagnetic valves and peristaltic pumps, converting the light signal into an electric signal, amplifying the electric signal and converting the electric signal into a digital signal so as to carry out data processing analysis, data display and communication between the instrument and a PC (Personal Computer). The full-automatic determining instrument is convenient to operate, rapid in measuring speed, high in precision and good in repeatability, and the information of the red blood cell osmotic fragility of the blood sample can be obtained through full-automatic detection.
Owner:广东华赢医疗科技有限公司

Recombinant bacterium and application of recombinant bacterium to generation of rebaudioside D by catalyzing rebaudioside A

The invention discloses a recombinant bacterium and application of the recombinant bacterium to the generation of rebaudioside D by catalyzing rebaudioside A. The recombinant bacterium contains a tomato-derived glycosyltransferase UGTSL2 gene and a potato-derived sucrose synthase StSUS1 gene; the tomato-derived glycosyltransferase UGTSL2 gene is cloned between NdeI and XhoI sites of pRSFDuet-1 to construct a recombinant plasmid pRSFDuet-SL2; then the potato-derived sucrose synthase StSUS1 gene is cloned between NcoI and EcoRI sites of the pRSFDuet-SL2 to construct a recombinant plasmid pRSFDuet-SL2-SUS1; the recombinant plasmid pRSFDuet-SL2-SUS1 is transferred into a host cell to obtain the recombinant bacterium. After the recombinant bacterium is subjected to induction expression, the recombinant bacterium is added into a reaction mixture to catalyze the rebaudioside A to generate the rebaudioside D; in reaction, crude enzyme liquid obtained by crushing the recombinant bacterium is utilized and separation and purification of an enzyme are avoided; lyophilized powder does not need to be produced; UDP (Uridine Diphosphate) or UDP-glucose and any cell penetration agent or other chemical reagents do not need to be added into a reaction solution, so that the recombinant bacterium has a better environment-friendly property. The yield of the rebaudioside D can reach 10.8g / L.
Owner:XINGHUA GL STEVIA CO LTD

Method for preparing rebaudioside M2 by catalyzing rebaudioside A through recombinant bacterium

The invention discloses a recombinant bacterium and application of the recombinant bacterium to preparation of rebaudioside M2 by catalyzing rebaudioside A. The recombinant bacterium contains a tomato-based glycosyltransferase UGTSL2 gene and a potato-based sucrose synthase StSUS1 gene at the same time; the tomato-based glycosyltransferase UGTSL2 gene is cloned between NdeI and XhoI sites of pRSFDuet-1 and is constructed to obtain a recombinant plasmid pRSFDuet-SL2; then the potato-based sucrose synthase StSUS1 gene is cloned between NcoI and EcoRI sites of the pRSFDuet-SL2 and is constructed to obtain a recombinant plasmid pRSFDuet-SL2-SUS1; the recombinant plasmid pRSFDuet-SL2-SUS1 is transferred into a host cell to obtain the recombinant bacterium. After the recombinant bacterium is subjected to induced expression, crude enzyme liquid is taken and is added into a reaction mixture to catalyze the rebaudioside A to generate the rebaudioside M2; in a reaction process, the crude enzyme liquid obtained by crushing the recombinant bacterium is utilized and separation and purification of an enzyme are avoided; lyophilized powder is also not needed and substrates including rebaudioside D and UDP or UDP-glucose and any cell penetration agent or other chemical reagents do not need to be added, so that the environmental friendliness is better. The yield of the rebaudioside M2 reaches 11.09g / L.
Owner:NANJING UNIV OF TECH
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