100 results about "Fusogenic peptide" 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.

Compositions and methods for improved delivery of macromolecules into eukaryotic cells are provided. Fusogenic peptides from fusion proteins of non-enveloped viruses enhance the efficiency of transfection of eukaryotic cells mediated by transfection agents such as cationic lipids, polycationic polymers such as PEI and dendrimers. These fusogenic peptides are used as part of a transfection complex that efficiently delivers a macromolecule, for example, a nucleic acid, into a eukaryotic cell. Novel cationic lipids and compositions of cationic lipids also are provided that may be used for the introduction of macromolecules such as nucleic acids, proteins and peptides into a variety of cells and tissues. The lipids can be used alone, in combination with other lipids and/or in combination with fusogenic peptides to prepare transfection complexes.

Genetically-encodable, environmentally-responsive fusion proteins comprising ELP peptides. Such fusion proteins exhibit unique physico-chemical and functional properties that can be modulated as a function of solution environment. The invention also provides methods for purifying the FPs, which take advantage of these unique properties, including high-throughput purification methods that produce high yields (e.g., milligram levels) of purified proteins, thereby yielding sufficient purified product for multiple assays and analyses. The high throughput purification technique is simpler and less expensive than current commercial high throughput purification methods, since it requires only one transfer of purification intermediates to a new multiwell plate.

The present invention provides improved cell delivery compositions. In particular, the invention provides biocompatible endosomolytic agents. In a preferred embodiment, the endosomolytic agents are also biodegradable and can be broken down within cells into components that the cells can either reuse of dispose of. In one aspect, the present invention provides endosomolytic agents capable of effecting the lysis of an endosome in response to a change in pH, and methods for effecting the lysis of an endosome. These inventive endosomolytic agents obviate the need for known agents (i.e., chloroquine, fusogenic peptides, inactivated adenoviruses and polyethyleneimine) that can burst endosomes and have negative effects on cells. In another aspect, the present invention provides cell delivery compositions comprising an endosomolytic component that is capable of effecting the lysis of the endosome in response to a change in pH, and an encapsulating, or packaging, component capable of packaging a therapeutic agent to be delivered to cellular or subcellular components.

The invention relates generally to the treatment and prevention of human cancer and viral diseases. More specifically, this invention relates to development of a new generation of vaccines that rely on eliciting cellular immune responses, specifically induction of cytotoxic T lymphocytes (CTL), against cancer cells and virus-infected cells via administration of a polymeric nanoparticle containing a vaccine comprising a fusion peptide or a modified peptide. Such a fusion peptide is composed of an insertion signal sequence and a peptide derived from a tumor antigen or a viral antigen, which improves antigen presentation and induces CTL with higher efficiency against cancer cells and virus-infected cells. An exemplary peptide utilized in the invention is Mart-1:27-35 peptide.

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 method is disclosed for encapsulating plasmids, oligonucleotides or negatively-charged drugs into liposomes having a different lipid composition between their inner and outer membrane bilayers and able to reach primary tumors and their metastases after intravenous injection to animals and humans. The formulation method includes complex formation between DNA with cationic lipid molecules and fusogenic/NLS peptide conjugates composed of a hydrophobic chain of about 10-20 amino acids and also containing four or more histidine residues or NLS at their one end. The encapsulated molecules display therapeutic efficacy in eradicating a variety of solid human tumors including but not limited to breast carcinoma and prostate carcinoma. Combination of the plasmids, oligonucleotides or negatively-charged drugs with other anti-neoplastic drugs (the positively-charged cis-platin, doxorubicin) encapsulated into liposomes are of therapeutic value. Also of therapeutic value in cancer eradication are combinations of encapsulated the plasmids, oligonucleotides or negatively-charged drugs with HSV-tk plus encapsulated ganciclovir.

A novel targeting peptide from the C-terminal of endothelin and/or a novel fusogenic peptide from hemagglutinin are optionally conjugated to the carboxy group of 1,2-dioleoyl-sn-glycero-3-succinate and incorporated into liposomes for therapeutic treatment. The novel targeting peptide directs liposomes to lung cells, and, therefore, is useful for delivering liposomes encapsulating cholinesterase genes, particularly, the human serum butyryl cholinesterase (Hu BChE) gene, as a treatment against nerve agents. It is emphasized that this abstract is provided to comply with the rules requiring an abstract which will allow a searcher or other reader quickly to ascertain the subject matter of the technical disclosure. It is submitted with the understanding that it will not be used to interpret or limit the scope or meaning of the appended issued claims. 37 CFR §1.72(b).

The invention discloses a helicobacter pylori ferritin-based novel coronavirus S protein double-region subunit nanovaccine. According to the invention, a receptor binding domain (RBD) of a virus and afusion peptide (FP) are jointly used as double antigens, and the double antigens are connected with a helicobacter pylori polymer protein (HP _ Ferritin) to form a fusion protein RBD-FP-HP _ Ferritin, so that antigen multimerization is realized; and then an eukaryotic cell expression system is utilized for expression, so as to form a 24-polymer nano antigen through the self-assembly action of HP_ Ferritin. According to the scheme, the defect that RBD monomers are insufficient in immunogenicity can be overcome, the obtained vaccine can remarkably improve the level of neutralizing antibodies of a host to viruses, and the generated antibodies have the capacity of strongly preventing the viruses from invading target cells. Moreover, the vaccine is simple in preparation method, easy to purifyand high in safety, and can be quickly applied to clinical tests.

The invention relates to a process for preparing and purifying Exendin-4 from colon bacillus, belonging to the field of genetic engineering. The purified Exendin-4 is obtained by cultivating Exendin-4 high-yielding engineering bacterial strain through bacteria, carrying out non-denatured affinity chromatography, and eliminating N-end fusogenic peptide with enterokinase. Compared with the prior art, the invention improves the formulations of lysate and eluent and adopts a gradient elution technique, thereby enhancing the yield and the purity of a target protein; and besides, the invention simplifies the operating procedures, is simple and easy to operate in operating steps and is suitable for large-batch industrial production.

Preparations of modified Fc fusion peptides that exhibit metabolically complete or near-complete oligosaccharide structures are provided. Also provided are methods for preparation of the modified Fc fusion peptides. These preparations exhibit enhanced serum half-life and are useful for treatment of a variety of diseases.

The invention discloses a dual-target tumor vaccine based on a tumor endothelium marker-8 gene and a preparation method thereof. The tumor vaccine is formed by combining an eukaryon expression vector recombined by the tumor endothelium marker-8 gene with fusogenic peptide obtained by fusing a membrane penetrating peptide HIV-Tat49-57 and a RGD peptide in the manner of non covalent bonds. The preparation method thereof comprises the following steps: respectively preparing the eukaryon expression vector recombined by the tumor endothelium marker-8 genethe and the fusogenic peptide obtained by fusing the membrane penetrating peptide HIV-Tat49-57 and the RGD peptide; and then, polymerizing the eukaryon expression vector and the fusogenic peptide through electrostatic interaction to form a compound. The tumor vaccine not only reserves the advantages of polypeptide vaccine, such as safety, easy preparation and purification and the like, but also overcomes the shortages, such as small polypeptide molecule, weak immunogenicity and difficult absorption by antigen presenting cells and the like. The vaccine can inhibit the tumor angiogenesis as well as induce the apoptosis of tumor cells, thereby greatly improving the effectiveness and the safety of tumor therapy. The vaccine has wide application prospects in the field of tumor therapy.

The invention discloses short chain polypeptide capable of promoting TFEB nuclear translocation, linear short chain polypeptide based on the short chain polypeptide, and an application of the short chain polypeptide to alleviating cerebral ischemia damage, and belongs to the technical field of biological pharmaceuticals. The short chain polypeptide disclosed by the invention is short chain polypeptide obtained through fusing function areas combined from TFEB protein and 14-3-3 protein, and the nucleotide sequence is as shown in SEQ.ID.NO.1. The invention further discloses the linear short chain polypeptide protecting the short chain polypeptide. The linear short chain polypeptide is obtained through fusing cell-penetrating peptide with the short chain polypeptide. Experiment verifies thatthe synthesized peptide can adjust and control TFEB nuclear translocation, and promote CMA to alleviate cell injury. Therefore, the invention discloses an application of the short chain polypeptide totreatment new target points for alleviating nerve cell death and improving cerebral ischemia damage.

The invention provides a polypeptide and an application thereof to preparation of medicament for treatment and/or prevention of tumor. An amino acid sequence of the polypeptide is shown in a sequence table SEQ ID No.1, or shown in the sequence table SEQ ID No.1 amino acid sequence with two or more amino acids substituted by unnatural amino acids with connectable side chains, and a derivative comprises a chimeric peptide formed by connection of the polypeptide and a cell-penetrating peptide, a fusogenic peptide formed by the polypeptide and a virus, a methylated polypeptide, a glycosylated polypeptide, and a pegylated polypeptide. The polypeptide or the polypeptide derivative can targetedly increase number of PML nucleosomes, and can be applied to preparation of medicament for treatment and/or prevention of tumor.

The invention discloses a compound of PSCA (Prostate Stem Cell Antigen) polypeptide and nucleic acid, which is a granular compound obtained by the way that through positive and negative charge attraction, a PSCA gene recombination eukaryotic expression vector is packaged by fusogenic peptide formed by a positive ion peptide DNA (Deoxyribonucleic Acid) transport carrier and HLA-A2 limit CTL (Cytotoxic T Lymphocyte) epitope peptide PSCA 14-22. The preparation method comprises the steps that in buffer salt solution with pH of 7.2-7.6, the fusogenic peptide and the PSCA gene recombination eukaryotic expression vector are added according to a certain positive and negative charge ratio, are then mixed, and are left standing under room temperature for 0.5-1.5 hours to obtain the compound; the compound is not only combined with the advantages of DNA vaccine and epitope peptide vaccine, but also can imitate natural virus to directly 'infect' APC (Antigen Presenting Cell) and other immune cells, so as to stimulate strong CTL response in vivo. The compound is expected to break down selftolerance of tumour antigen, can be used to prepare prostate cancer therapeutic vaccine of more than 50 % of population in China, and has potential and good development and application prospect in the prostate cancer immunization therapy field.

The invention relates to a hepatitis B virus multi-epitope fusion protein and a preparation method and application thereof. The fusion protein is obtained by inserting hepatitis B virus multi-epitope fusion peptide (with the sequence shown as SEQIDNo.1) formed by serially connecting HBsAg313-321, HBsAg335-343, Pol150-159, Pol455-463 and Padre epitopes through connecting peptide between amino acidat the 78th position and amino acid at the 79th position of a hepatitis B virus core protein; and the preparation method comprises the following steps of: constructing a hepatitis B virus multi-epitope fusion protein expression plasmid pET28-HBc-HP; performing isopropyl thiogalactoside (IPTG) inducing expression by using an Escherichia coli expression system; and purifying by using affinity chromatography. The fusion protein carries a plurality of supertype epitopes of hepatitis B surface antigen (HBsAg), hepatitis B core antigen (HBcAg) and polymerase, is viral particles, has the advantages of strong immunogenicity, wide applicable range and the like, and can be used for preparing therapeutic hepatitis B vaccines.

The present invention belongs to the field of molecular immunology, discloses six antigen epitope molecule simulating peptides capable of exciting human body's tubercle bacillus antagonizing protective immunoreaction, and provides recombinant tubercle bacillus antigen polyepitope peptides, which are fusion peptides with the amino acid sequences as shown in SEQ ID No.1, SEQ ID No. 2, SEQ ID No. 3, SEQ ID No. 4, SEQ ID No. 5 and SEQ ID No. 6 separately. The present invention also provides their construction process and use. These polyepitope peptides, cell and animal experiments show, can excite efficient specific tubercle bacillus antagonizing protective immune response. The present invention may be used in preventing and treating tuberculosis.