56 results about "Nuclear localization sequence" patented technology

The present invention is directed to protocells for specific targeting of hepatocellular and other cancer cells which comprise a nanoporous silica core with a supported lipid bilayer; at least one agent which facilitates cancer cell death (such as a traditional small molecule, a macromolecular cargo (e.g. siRNA or a protein toxin such as ricin toxin A-chain or diphtheria toxin A-chain) and/or a histone-packaged plasmid DNA disposed within the nanoporous silica core (preferably supercoiled in order to more efficiently package the DNA into protocells) which is optionally modified with a nuclear localization sequence to assist in localizing protocells within the nucleus of the cancer cell and the ability to express peptides involved in therapy (apoptosis/cell death) of the cancer cell or as a reporter, a targeting peptide which targets cancer cells in tissue to be treated such that binding of the protocell to the targeted cells is specific and enhanced and a fusogenic peptide that promotes endosomal escape of protocells and encapsulated DNA. Protocells according to the present invention may be used to treat cancer, especially including hepatocellular (liver) cancer using novel binding peptides (c-MET peptides) which selectively bind to hepatocellular tissue or to function in diagnosis of cancer, including cancer treatment and drug discovery.

A nanoparticle delivery vehicle, comprising a nanoparticle, an active agent and a nuclear localization signal and methods of modulating gene expression and protein expression employing the nanoparticle delivery vehicle. A representative method includes providing a nanoparticle delivery vehicle comprising a nanoparticle having a diameter of about 30 nm or less, an active agent and a nuclear localization signal; and contacting a target cell with the nanoparticle delivery vehicle, whereby an active agent is delivered to the nucleus of a target cell. Another representative method includes providing a nanoparticle delivery vehicle comprising a nanoparticle having a diameter greater than or equal to about 30 nm, an active agent and a nuclear localization signal; and contacting a target cell with the nanoparticle delivery vehicle, whereby an active agent is delivered to the cytoplasm of a cell.

A biodegradable cross-linked cationic multi-block copolymer of linear polyethylenimine (LPEI) wherein the LPEI blocks are linked together by hydrophilic linkers with a biodegradable disulfide bond and methods of making thereof. The biodegradable cross-linked cationic multi-block copolymer may also contain pendant functional moieties which are preferably receptor ligands, membrane permeating agents, endosomolytic agents, nuclear localization sequences, pH sensitive endosomolytic peptides, chromogenic or fluorescent dyes.

The present invention is directed to protocells for specific targeting of hepatocellular and other cancer cells which comprise a nanoporous silica core with a supported lipid bilayer; at least one agent which facilitates cancer cell death (such as a traditional small molecule, a macromolecular cargo (e.g. siRNA or a protein toxin such as ricin toxin A-chain or diphtheria toxin A-chain) and/or a histone-packaged plasmid DNA disposed within the nanoporous silica core (preferably supercoiled in order to more efficiently package the DNA into protocells) which is optionally modified with a nuclear localization sequence to assist in localizing protocells within the nucleus of the cancer cell and the ability to express peptides involved in therapy (apoptosis/cell death) of the cancer cell or as a reporter, a targeting peptide which targets cancer cells in tissue to be treated such that binding of the protocell to the targeted cells is specific and enhanced and a fusogenic peptide that promotes endosomal escape of protocells and encapsulated DNA. Protocells according to the present invention may be used to treat cancer, especially including hepatocellular (liver) cancer using novel binding peptides (c-MET peptides) which selectively bind to hepatocellular tissue or to function in diagnosis of cancer, including cancer treatment and drug discovery.

The invention provides methods of determining the presence of a nuclear localization signal and/or the presence of a nuclear export signal in a protein of interest. The invention further provides chimeric nucleic acids and recombinant host cells for use in such methods. Additionally provided is a nucleic acid molecule encoding a modified LexA protein, wherein the modified LexA protein has no nuclear localization signal, as well as the modified LexA protein itself. In the nuclear import assay, if a protein of interest fused to a mLexA-Gal4AD hybrid contains a functional NLS, the fusion product will enter the yeast cell nucleus and activate the expression of reporter genes. In the nuclear export assay, if a protein of interest fused to a mLexA-SV40 NLS-Gal4AD hybrid contains a functional NES, the fusion product localized to the cell nucleus will exit into the cytoplasm, decreasing the reporter gene expression levels.

The invention relates to an artificial transcription factor comprising a polydactyl zinc finger protein targeting specifically a receptor gene promoter fused to an inhibitory or activatory protein domain, a nuclear localization sequence, and a protein transduction domain. In particular examples these receptor gene promoters regulate the expression of the endothelin receptor A, the endothelin receptor B, the Toll-like receptor 4 or the high-affinity IgE receptor. Artificial transcription factors directed to the endothelin A or B receptors are useful in the treatment of diseases modulated by endothelin, such as cardiovascular diseases, and, in particular, eye diseases, e.g. retinal vein occlusion, retinal artery occlusion, macular edema, optic neuropathy, central serous chorioretinopathy, retinitis pigmentosa, Leber's hereditary optic neuropathy, and the like. Artificial transcription factors directed to the Toll-like receptor 4 or the IgE receptor are useful for the treatment of autoimmune disorders, and the like, and allergic disorders, respectively.

The present invention is directed to a transformation system for making transgenic organisms that includes a vector containing a modified piggyBac transposon into which is inserted an enhanced green fluorescent protein gene linked to a polyubiquitin promoter sequence and a nuclear localizing sequence; and a helper transposase vector that includes an hsp70 promoter sequence upstream of the putative piggyBac promoter that increases the transformation frequency of this system.

The present invention concerns alkyl aryl carbonyl compounds that possess anti-infective activity. The compounds of the invention can be used to target specific nuclear localization signal, thereby blocking importation of specific proteins or molecular complex into the nucleus of a cell. The invention encompasses methods of use of such compounds for treatment or prevention of infectious diseases, such as parasitic and viral diseases, including, for example, malaria and acquired immunodeficiency syndrome. The use of the compounds to detect certain specific protein structures which are present in nuclear localization sequences is also taught.

The invention discloses a non-viral gene vector constructed on the basis of N-terminal octadecane acylated antibacterial peptide. The vector utilizes the characteristics of melittin, i.e. endosome-destroying activity and membrane penetrating activity, moreover, a nuclear localization sequence and a polyarginine sequence are added into the melittin sequence, and then a series of forward and reverse analogues are synthesized, and octadecanoic acid is connected with the N terminals of the obtained analogues, so that the analogues and plasmid DNA (deoxyribonucleic acid) form stable nano-particles. An experiment result shows that because the non-viral gene vector constructed on the basis of N-terminal octadecane acylated antibacterial peptide has higher transfection efficiency and lower cytotoxicity and the polypeptide vector is easy to biodegrade, the non-viral gene vector is more suitable for application in vivo.

The invention discloses saccharomyces cerevisiae engineering bacteria with low-yielding ethyl carbamate. A regulatory factor G1n3p in saccharomyces cerevisiae is transformed through engineering bacteria. The concrete strategy is that a phosphorylation site on a G1n3p nuclear localization sequence is subjected to mutation to form three phosphorylation sites on the G1n3p nuclear localization sequence; the three phosphorylation sites respectively are the 344th, 347th and 355th serine. In order to obtain a better technical effect, a nuclear localization regulatory region of combining G1n3p with an upstream regulatory factor can be further removed; the G1n3p of a regulatory sequence at the tail end of C is removed by truncated expression, wherein an expression sequence is 1-653. The EC yield of the engineering bacteria disclosed by the invention is reduced by 62% by detection of a yellow rice wine simulation system. In addition, the content of main ingredients is not significantly changed, and the fermentation characteristics and the growth characteristics of a bacterial strain are not affected after the content of other ingredients in a fermentation liquor after fermentation is detected.

The invention belongs to the field of microbial genetics and molecular biology and discloses a method with a function of reducing accumulation of ethyl carbamate in rice wine fermentation. Genetically engineered bacteria modified by nitrogen catabolite repression regulation factors are adopted for rice wine fermentation, and engineered saccharomyces cerevisiae eliminates nuclear localization regulatory sequences of the regulation factors Gln3p and Gat1p and mutates phosphorylation sites of the nuclear localization sequences. In a simulated rice wine fermentation system, compared with rice wine with wild strains for fermentation, rice wine fermented with the genetically engineered bacteria has the advantages that contents of carbamide and ethyl carbamate in the rice wine are decreased by 63% and 72% respectively, the content of the ethyl carbamate in the rice wine is decreased to about 55.53 microgram/L, and contents of major nutrient substances and characteristic flavor substances are less in difference. Therefore, the method has a huge potential of application to rice wine production.

Disclosed are novel cell-penetrating transporters for enhancing cellular uptake of peptide fusion proteins into live cells. The cell-penetrating transporters comprise a functionalized peptide construct comprising a cell importation peptide covalently bound to a cargo, the cell importation peptide in an unreactive monomeric form, and a pharmaceutical carrier. In certain embodiments, the cargo further comprises a nuclear localization sequence (NLS) allowing the cargo to be transported across the nuclear membrane.

The invention relates to a tonoplast localization sequence and its application. The inventor, for the first time, separates a segment of signal sequence for specific location of cell tonoplast, i.e. a tonoplast targeting sequence (TTS). The sequence can lead accurate and efficient location of protein on intracellular tonoplast. The sequence can be utilized to perform localization transformation on target protein, and expression of the target protein at other sites other than the tonoplast can be reduced or prevented.

The invention discloses a porcine circovirus type 2 Cap gene modified recombinant antigen and an application thereof, and belongs to the field of veterinary vaccine researches. The modified recombinant antigen is obtained by modification and construction of a Cap gene after a nuclear localization sequence of a porcine circovirus type 2 LG strain widely prevalent in swinery in China at present is deleted. A vaccine prepared from the modified recombinant antigen can stimulate organisms to produce high-level neutralizing antibodies, is superior to commercially available inactivated influenza virus vaccines and separate Cap protein immunization groups after nuclear localization sequences are deleted, has a highest antibody level, is safe and harmless to immunized animals after inoculation, has the advantages of low price, safety, stability, high yield and easiness in preservation and application, and has great significance to related diseases caused by porcine circovirus type 2 infection in China, so that the porcine circovirus type 2 Cap gene modified recombinant antigen has a good application prospect.

The invention relates to an artificial transcription factor comprising a polydactyl zinc finger protein targeting specifically the OPA1 promoter fused to an activatory protein domain, and a nuclear localization sequence. Artificial transcription factors directed against the OPA1 promoter are useful for the treatment of diseases associated with OPA1 haploinsufficiency, such as autosomal dominant optic atrophy, syndromic autosomal dominant optic atrophy plus and normal tension glaucoma.

The invention relates to the biological field, specifically relates to detection techniques of proteins and particularly relates to a detection method for a retinoic acid receptor alpha protein with a nuclear localization signal. The detection method is a laser scanning confocal method and comprises the following steps of putting a dyed target cell into a two-tone fluorescence channel with the adequate wavelength of a laser scanning confocal microscope to capture fluorescence strength data of each part in the target cell, and analyzing the fluorescence strength data of each part in the target cell so as to judge whether the retinoic acid receptor alpha protein with the nuclear localization signal exists in the target cell. Besides, according to the detection method, multiple methods for detecting the NLS-RAR alpha (nuclear localization signal-retinoic acid receptor alpha) protein are integrated to lay the foundation for further research on the early diagnosis and recurrence monitoring of acute promyelocytic leukemia.

The invention discloses a double-targeting chimeric peptide and an application thereof in preparation of an anti-tumor metastasis drug. The chimeric peptide has an amino acid sequence shown in SEQ ID NO.1, acts on CXCR4+ tumor cells in a targeting manner, performs synergistic inhibition of a CXCR4/SDF-1a functional axis and an NF-kB signaling pathway in the tumor cells, and reduces CXCR4+ tumor cell migration and invasion abilities. Specifically, the chimeric peptide is formed by engomphosis of an SDF-1a N-terminal sequence and a nuclear localization sequence (NLS) of an NF-kB P50 subunit; a tumor cell surface receptor CXCR4 is identified through the N-terminal sequence in a targeting manner, and the intracellular SDF-1a/CXCR4 function axis role is inhibited; and the chimeric peptide also as a membrane penetrating peptide promotes the NF-kB P50 subunit NLS sequence to effectively enter the tumor cells, inhibits NF-kB nuclear import transcription process in a targeting manner, and has important value in study of multi-target antitumor metastasis drugs.

The present invention provides for a synthetic transcription factor (TF) comprising (a) a DNA-binding domain of a transcription factor linked to (b) an activator domain or repressor domain, and (c) a nuclear localization sequence (NLS).

Disclosed are a pharmaceutical composition containing plasmid DNA, characterized by that it comprises plasmid DNA as active ingredients; a peptide comprising a nuclear localization signal (NLS) sequence or RGD peptide sequence; a cationic compound; and an amphiphilic copolymer, and the plasmid DNA binds to a peptide to form a complex with the cationic compound and the complex is entrapped in the nanoparticle structure of the amphiphilic block copolymer, and a preparation method thereof.