223 results about "Molecular targeting" patented technology

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.

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.

Compositions for targeted mutagenesis of cell surface receptors for HIV and methods of their use are provided herein. The compositions include triplex-forming molecules that bind to duplex DNA in a sequence specific manner at target sites to form triple-stranded structures. The triplex-forming molecules can be triplex-forming oligonucleotides (TFOs) or peptide nucleic acids (PNAs). The triplex-forming molecules are useful to induce site-specific homologous recombination in mammalian cells when used in combination with donor oligonucleotides. The triplex-forming molecules target sites within or adjacent to genes that encodes cell surface receptors for human immunodeficiency virus (HIV). This binding stimulates homologous recombination of a donor oligonucleotide to cause mutations in HIV cell surface receptor genes that result in one or more deficiencies in the ability of the encoded receptor to bind to HIV and allow its transport into the cell. Methods for ex vivo and in vivo prophylaxis and therapy of HIV infection using the disclosed compositions are also provided.

The invention discloses a thieno 2,4-substituted pyrimidine compound of which the general formulas are (I), (II), (III) and (IV), or pharmaceutically acceptable salt or stereisomer or a prodrug molecule, and a pharmaceutical composition and application thereof. The thieno 2,4-substituted pyrimidine compound can effectively restrain abnormal expression of Aurora kinase, has specific inhibited effect on Aurora-A and Aurora-B, can be applied to a novel field of molecular targeting treatment, and has strong inhibitory activity on an excessive hyperplasia disease, especially cervical tumor cells, human macrophage line leukemia cell, and human t-lymphocyte line cancer cell.

The purpose of this invention is to provide an agent useful for prevention and / or treatment of psychosis, schizophrenia and cognitive impairments. To solve this problem, this invention provides epidermal growth factor receptor inhibitors as therapeutic agents for psychosis, schizophrenia and cognitive impairments.

Novel blood-brain barrier permeant amyloid-targeting peptides and peptide conjugates are described. The peptide conjugates include a radioisotope or other label in a stable complex that translocates across brain capillary endothelial cell monolayers. The labeled peptide conjugate binds to amyloid plaques (Aβ) associated with Alzheimer's disease, and is useful for the targeted delivery of therapeutic and diagnostic molecules into the brain.

The invention provides a kit for detecting the epidermal growth factor receptor (EGFR) mutation by a primer specific fluorescence polymerase chain reaction (PCR), in particular to the diagnosis of the EGFR gene mutation in tumor tissues and peripheral blood serums of tumor patients. Aiming at specific mutant sites relative to the curative effects of molecular targeted anti-cancer drugs, the kit is provided with a specific oligonucleotide primer sequence and a probe sequence, carries out fluorescence PCR detection respectively through a wild type PCR system and a mutation type PCR system on each sample to be detected and judges whether the samples have the mutation of EGFR19 exons and 21 exons or not through the magnitude of a difference value (delta Ct) of Ct values of two times of reaction. The kit can detect whether the specific sites of the EDFR have the mutation or not and can be used for the curative effect forecast of new molecular targeted anti-cancer drugs and the guidance of clinical individualized medicine application programs of the tumor patients.

The present invention relates to therapeutic agents useful for the treatment of Severe Acute Respiratory Syndrome (SARS) in humans. In particular, the present invention relates to RNA interference (RNAi) molecules useful for inhibiting the infection and replication of hSARS virus. Preferably, the RNAi molecules target the replicase region of the hSARS virus, or combinations of different sites of hSARS virus genes. The present invention further encompasses methods of using the RNAi molecules for preventing and / or treating SARS. Vaccines and kits comprising therapeutically effective amounts of the RNAi molecules are also encompassed.

The invention discloses glycosylated boron dipyrromethene fluorophore derivatives as well as a preparation method and application of the glycosylated boron dipyrromethene fluorophore derivatives. The method comprises the following steps: by taking glucose and glucosides thereof as action targets, connecting covalent bonds of the action targets to boron dipyrromethene fluorophore derivatives for photodynamics therapy, so that a third generation photosensitizer against cancer which can be used for targeted therapy is obtained. The dipyrromethene fluorophore derivatives containing glucose and glucosides are taken as study researches, activity study of in-vitro breast cancer-resistant cells MBA-MD-231 is expanded, a prodrug suitable for molecular targeted therapy is screened, and a foundation is laid for applying the glycosylated boron dipyrromethene fluorophore derivatives to targeted therapy of cancers. Moreover, the compound synthesis method is simple, readily available in raw materials, low in cost, few in side reactions, high in yield and simple in purification, and industrial production is promoted.

The present invention provides compositions useful for the treatment of cancer that inhibit tumor stem cells through suppression of an activity or the expression of BORIS. The compositions target tumor stem cells through molecules that are specific to tumor stem cells. Specifically, the invention provides immunoliposomes specific to tumor stem cells that include nucleic acid compositions capable of eliciting the process of RNA interference of BORIS expression. Also provided are immunoliposomes specific to tumor stem cells that include anti-BORIS ribozymes, antisense oligonucleotides, decoy oligonucleotides or small molecule inhibitors. Methods of manufacturing, delivering, and use of such compositions in the treatment of cancer are also provided.

The invention provides a peptide radioactive medicine comprising an iRGD sequence. The sequence of the peptide comprises CRGDKGPDC or CRGDRGPDC or CRGDKGPEC and is formed by marking through coupling radioactive metal nuclides or positron nuclides, the peptide radioactive medicine comprising the iRGD sequence has three functions of molecular target integrin alpha v beta 3 receptor, Neuropilin-l receptor and cellular transduction, and the peptide radioactive medicine comprising the iRGD sequence can be used as a diagnostic medicine capable of greatly increasing the target / non-target ratio, so that the sensitivity can be effectively improved, and the development quality can be improved, and the peptide radioactive medicine can be used as a therapeutic medicine capable of obviously improving the treatment effect.

The invention discloses a double-targeting polypeptide-antibody-drug conjugate, and a prepared method and antineoplastic application thereof. The double-targeting polypeptide-antibody-drug conjugate structurally includes four components of (A), tumor specificity targeting polypeptide; (B), an antineoplastic drug; (C), a mitochondria target functional group; and (D), hydrazone bonds used for connecting the polypeptide and the antineoplastic drug. The tumor specificity targeting polypeptide is connected with the antineoplastic drug by a connecting arm comprising the hydrazone bonds; the antineoplastic drug is connected with the mitochondria target functional group by chemical bonds; and the tumor specificity targeting polypeptide is suitable for targeting the conjugate to a tumour cell and marker protein LAPTM4B carried on the surface of the tumour cell is used as a specificity target. A molecular target is combined with an organelle target, selective uptake of the drug in the tumour cell can be increased, an acting site of a DOX drug can be transferred form cell nucleus to mitochondria, and therefore the condition that the tumour cell is killed by drug resistance is avoided.

Disclosed are methods of treating subjects having disorders or conditions characterized by an unwanted immune response including administering an effective amount of an early activation molecule agonist, antagonist or depletor, to the subject. Human monoclonal antibodies specific to the early activation molecules, and methods of use, are also disclosed.

The invention relates to a novel magnetic molecular targeted ultrasound contrast agent, in particular to a gas-wrapped magnetic liposome microsphere suspension with the mean diameter of 1-4 micrometers and a preparation method thereof. The preparation method of the magnetic molecular targeted ultrasound contrast agent microsphere comprises a condition that a lipid layer of the microsphere and / or the surface of the lipid layer contains (or connects) magnetic response materials. A contrast agent microsphere wall material contains phospholipids, polyethylene glycol (PEG), PEG phospholipid polymers, biotinylated and / or polypeptide modificatory PEG phospholipid polymer, poloxamer, ligands (monoclonal antibodies or polypeptide, and the like) and the magnetic response materials and / or avidin bridging materials, wherein the ligand (monoclonal antibodies or polypeptide, and the like) has specific affinity to target molecules, the wrapped gas is a fluorine carbon gas, and a solvent is an aqueous medium (distilled water). The invention also provides the preparation method of the magnetic molecular targeted ultrasound contrast agent microsphere, which comprises a condition that the specific ligand is connected with the microsphere in a covalence and avidin bridging way. The novel magnetic molecular targeted ultrasound contrast agent has good targeted developing effect, can be used for evaluating the change of vessel endothelial molecules of an arterious and venous system of an organic tissue and has good application prospect in treatment.

The invention relates to a water-soluble molecular target porphin photosensitizer and a preparation method thereof. The photosensitizer is characterized in that the two bridged ends of polyethylene glycol (PEG) diamine are respectively connected with folic acid and porphin with substituent groups, wherein other substituent groups can be connected with the porphin, and the average molecular weight of PEG is 1000-10000. According to the preparation method of the water-soluble molecular target porphin photosensitizer, PEG diamine reacts with folic acid so as to produce PEG amine which is obtained from single folic acid, and the PEG amine has amidation with carboxyl, acyl chloride or anhydride substituent group on the porphin so as to obtain the porphin-PEG-folic acid target photosensitizer. The photosensitizer has good photodynamic activity, tumor target performance and good water solubility and is applicable to intravenous administration; the phagocytosis of macrophage to the photosensitizer can be reduced, the body circulation time of the photosensitizer is prolonged and the bioavailability of the photosensitizer is improved. Moreover, the preparation method of the water-soluble molecular target photosensitizer is simple to operate, has moderate conditions and has strong repeatability.

The invention provides a fixing method of targeted primer in single-molecule targeted sequencing, a single-molecule targeted sequencing reagent box and application. The fixing method includes: (1), soaking a substrate into fixing liquid containing 0.4-3.2nM of the targeted primer, and then cleaning the substrate, wherein the targeted primer is a primer sequence with 10-30bp of polyT at a 5' end, and the primer sequence is a sequence complementary with at least part of sequence of template nucleic acid; (2), soaking the cleaned substrate into phosphate passivation liquid for passivation, and then cleaning the substrate to obtain the substrate with the targeted primer fixed on the surface. The fixing method is simple to operate, and fixing density of the targeted primer is uniform and is about 3000 points per visual field.

The invention discloses a short interfering ribonucleic acid (siRNA) molecule for promoting scarless healing of skin wounds, a cocktail combination of a plurality of siRNA molecules targeting a plurality of related genes of scarless healing of wounds, and a pharmaceutical composition taking the siRNA molecule or the cocktail combination thereof as an active ingredient. Proven by cell experiments and mouse and pig skin wound models, the pharmaceutical composition can promote scarless healing of skin wounds resulted from traumata, surgical operation, or diabetes skin ulcer and the like, wherein the siRNA molecule can target genes causing pathological repair of wounds or adverse reactions; the siRNA double chains have different lengths and different tail ends and can target a homologous sequence of the same gene of cells of human, mouse and pig; the plurality of siRNAs in the cocktail combination can simultaneously inhibit various related genes of wound inflammation and revascularization, and has more obvious drug effects; and pharmaceutical carriers such as histidine-lysine polymer, dendritic polymer or liposome and the like in the pharmaceutical composition in a nanoparticle form can enhance the siRNA to be introduced into the skin tissue.

The invention discloses a composition for treating eye diseases by double-target / multi-target small nucleic acid and applications of the composition. The composition comprises two small nucleic acid molecules and a medicinal carrier, target genes of the two small nucleic acid molecules are selected from two of VEGF (vascular endothelial growth factor) gene, VEGFR2 (vascular endothelial growth factor receptor2) gene and TGF-b1 (transforming growth factor-beta1) gene; or the composition comprises three small nucleic acid molecules and a medicinal carrier, and target genes of the three small nucleic acid molecules are respectively VEGF gene, VEGFR2 gene and TGF-b1 gene. The composition can be used for effectively treating eye diseases by virtue of ribonucleic acid interference (RNAi) mediated inhibitor gene expression and biochemical pathway, and can be prepared to form a medicament for treating eye diseases, including proliferatived diabetic retinophathy, diabetic macular edema, herpes simplex interstitial keratitis, age-related macular degeneration, uveitis and the like.

The invention discloses a bilateral biotin-phthalocyanine zinc conjugate as well as preparation and application thereof. According to the conjugate disclosed by the invention, a biotin-cell growth-promoting factor (which is a critical micronutrient for cells to maintain normal functions, growth and reproduction) is used as a tumor target and is covalently connected onto a phthalocyanine zinc photosensitizer capable of being used for a photodynamic therapy, thus obtaining a third-generation anti-cancer photosensitizer for targeted therapy. Meanwhile, according to the conjugate, the biotin instead of a phthalocyanine zinc derivative acts a research object, human breast cancer cell MCF-7 and human embryo lung inoblast HELF act as subject cell lines respectively, a research regarding the in-vitro anti-cancer activity of the biotin is developed, and a prodrug suitable for a molecular targeted therapy is screened out, and a foundation is laid for applying the biotin instead of the phthalocyanine zinc derivative to the targeted therapy of cancers. The compound, namely the conjugate disclosed by the invention, is relatively simple in synthesis method, easily available in raw materials, low in cost, fewer in side reactions, relatively high in yield, easy to purify and beneficial for industrial production.

The invention discloses a function of HOXD-AS1 in diagnosis and treatment of esophageal squamous carcinoma and relates to discovery, detection and application of long-chain noncoding RNA. According to the sequences of the long-chain noncoding RNA, a specific real-time quantitative PCR primer is designed and synthesized; a real-time quantitative PCR preparation is utilized to detect the expression level of the long-chain noncoding RNA in a clinical case specimen of the esophageal squamous carcinoma, and results show that the expression of the long-chain noncoding RNA in the esophageal squamous carcinoma is remarkably up-regulated and the expression level of the long-chain noncoding RNA is highly associated with both clinical stages and pathological N stages of an esophageal squamous carcinoma patient. The specific detection sequences disclosed by the invention are expected to be used for preparing the preparation for auxiliary diagnosis, curative effect prediction or prognosis judgment of the esophageal squamous carcinoma. In addition, two siRNA sequences for specifically knocking down the expression of the long-chain noncoding RNA are designed and synthesized; an experiment proves that after the expression level of the long-chain noncoding RNA is specifically knocked down in a human esophageal squamous carcinoma cell strain, the quantity of migrated tumor cells is remarkably reduced; therefore the siRNA sequences disclosed by the invention is also expected to be used as a molecular targeting treatment tool for inhibiting the cell migration rate of the esophageal squamous carcinoma.

siRNA and antisense reagents capable of blocking expression of the IGF-1 receptor.

Novel blood-brain barrier permeant amyloid-targeting peptides and peptide conjugates are described. The peptide conjugates include a radioisotope or other label in a stable complex that translocates across brain capillary endothelial cell monolayers. The labeled peptide conjugate binds to amyloid plaques (Aβ) associated with Alzheimer's disease, and is useful for the targeted delivery of therapeutic and diagnostic molecules into the brain.

The invention discloses a molecular targeting anticancer photosensitizer phthalocyanine-erlotinib yoke compound, and preparation and application thereof. Erlotinib with a long alcoxyl chain is introduced at the periphery of a metal phthalocyanine ring, so that the amphipathy, the bioco mpatibility and the targeting effect of the photosensitizer can be increased. The yoke compound is not easily gathered, which is favorable for improvement of the cell uptake rate; meanwhile, since the compound is single in structure and no isomer exists, the product is easily purified. By adopting the compound, the targeting effect of the photosensitizer in photodynamic therapy is expected to be improved; and meanwhile, the activity of the photosensitizer in the photodynamic therapy is enhanced. The synthesis method of the phthalocyanine-erlotinib yoke compound is simple, involves less side reactions, is high in yield and low in cost; moreover, the raw materials are easily available. Therefore, industrial production is facilitated.

The invention discloses a synthesis method of crizotinib serving as an antitumor molecular targeting medicament, which belongs to the field of pharmacy and relates to a novel splitting process of a chiral isomer of a crizotinib precursor and a synthesis method of an intermediate. (S)-1-(2,6-dichloro-3-fluorophenyl)ethanol is prepared by splitting a 1-(2,6- dichloro-3-fluorophenyl)ethanol racemic body into S-alcohol and R-alcohol with a catalytic splitting method for combining Boc-L-proline(N-tert-butoxycarbonyl-L-proline), paratoluenesulfonic acid serving as a catalyst and 1-(3-dimethylaminopropyl)-3-ethyl carbodiimide hydrochloride, separating and purifying; the yield is 60 percent; and the excessive fraction ee) of the chiral enantiomer is 99 percent. According to the method, time is shortened, cost is reduced, the generation of waste acids is avoided, environmental pollution is lowered, column chromatography isolation is not required, and industrial production is easier to implement.

The invention relates to the technical field of biology, in particular to a leukemia mouse model based on a gene co-transfection technology and a preparation method thereof. The preparation method of the leukemia mouse model comprises the following steps: performing construction and packaging of K-ras mutants and AML1-ETO fusion gene lentivirus vectors; performing bone marrow cell separation and virus infection condition monitoring; implanting infection cells in a mouse to build a leukemia animal model; and performing model identification. The method of building the leukemia mouse model in a mode of utilizing caudal vein injection to lead in the manual site-directed mutagenesis K-ras mutants and AML1-ETO fusion gene lentivirus vectors is adopted initiatively. The leukemia mouse model is high in success rate, pathological characteristics are high in similarity to morbidity conditions of clinical leukemia, and the novel animal model can be provided for leukemia extramedullary infiltration mechanism research, leukemia medicine screening and gene and molecule target treatment.

The invention discloses a receptor molecularly-targeted imaging agent and a preparation method and application thereof. The receptor molecularly-targeted imaging agent comprises a polyethylene glycol short chain which is linked with 17alpha-ethinyloestradiol of a target estrogen receptor through 'click' reaction. The receptor molecularly-targeted imaging agent is shown as a concrete general molecular formula in the description, wherein the 17alpha-ethinyloestradiol serves as a targeting group, polyethylene glycol serves as a hydrophilic group, and <18>F serves as a radioactive group. The receptor molecularly-targeted imaging agent has excellent biological properties and high specificity, is high in uptake when used in positive breast cancer tumors of the estrogen receptor and capable of distinguishing between estrogen positive receptors and estrogen negative receptors, and meets the conditions as a breast cancer receptor imaging agent.

The invention discloses a novel fusion gene for MiT familial translocation renal cell carcinoma and a detection primer and application of the novel fusion gene. The gene is a PRCC-MITF fusion gene, and is formed by fusing a PRCC exon 5 and an MITF exon 4. A PCR primer for detecting PRCC-MITF translocation tumors comprises an upstream primer as shown in SEQ ID NO. 1 and a downstream primer as shown in SEQ ID NO. 2. The specific PCR primer is designed for the novel fusion gene discovered by high-throughput sequencing, the detection range of the original detection means is expanded, the novel fusion gene is applied to clinical application, and the detection ratio and accuracy rate of the MiT familial translocation renal cell carcinoma can be improved. The novel fusion gene provides a basis for diagnostic typing and molecular targeting treatment.