| 摘要 |
<p>#CMT# #/CMT# Composition comprises a virus-like particle, which is built from more molecules of viral capsid proteins and contains a RNA-interference-inducing molecule. #CMT# : #/CMT# Independent claims are included for: (1) producing the composition, comprising assembling the viral capsid protein to virus-like protein in the presence of RNA-interference-inducing molecules; (2) introducing RNA-interference-inducing molecule into a target cell, comprising assembling the viral capsid protein to virus-like protein in the presence of the RNA-interference-inducing molecule, contacting the virus-like protein loaded with the RNA-interference-inducing molecules with the target cells under the condition in which an absorption of the RNA-interference-inducing molecules takes place into the target cells; (3) down regulation of at least a gene in the target cell, comprising providing the composition, contacting the composition with the target cell under the condition in which an absorption of the RNA-interference-inducing molecule takes place into the target cell; (4) a test kit for introducing the RNA-interference-inducing molecule into the target cells, comprising the composition; (5) a pharmaceutical composition comprising virus-like protein and RNA-interference-inducing molecule and optionally standard buffer, auxiliary materials, additives and/or diluting agents; (6) a modified polyoma JC virus-VP1 capsid protein comprising nuclear localization signal so that coding of nucleic acid or virus-like protein composition containing the modified capsid protein, takes place; (7) a virus-like protein composition, where the virus-like protein contains an immunostimulatory nucleic acid optionally in combination with polypeptide- or peptide-immunogen, an aptamer or a small interfering DNA molecule; and (8) a polyoma JC virus-VP1 capsid protein at which at least a heterologous binding partner e.g. a polypeptide, is bound over the amino acid residue lys-60 and/or lys-164. #CMT#ACTIVITY : #/CMT# None given. #CMT#MECHANISM OF ACTION : #/CMT# Gene therapy. #CMT#USE : #/CMT# The composition is useful for introducing RNA-interference-inducing molecule into a target cell, preferably into a eukaryotic cell, preferably a mammary cell of human origin, where in the target cell: the expression of at least a gene is correlated with a pathological condition; at least a gene, which is formed from a pathogenic virus, is expressed; the expression of at least an endogenous gene is increased; and the increased expression of the endogenous gene is correlated with a pathological condition. The composition or the pharmaceutical composition is useful: as a medicament; and for producing a medicament for the diagnosis, prevention and/or treatment of diseases or disease conditions, which are caused by expression of a nucleic acid, which is formed from a pathogenic organisms, or by increased or unwanted expression of an endogenous genes. No biological data given. #CMT#ADVANTAGE : #/CMT# The composition is effective for in-vivo and in-vitro transferring of the cell specific therapeutic gene into the eukaryotic cells without affecting its integrity of the cellular genome. #CMT#BIOLOGY : #/CMT# Preferred Components: The RNA-interference-inducing molecule is: a RNA and/or a RNA-analog; and a DNA and/or a DNA-analog. The RNA is small interfering RNA, micro-RNA, double-stranded RNA, small hairpin RNA or their precursors. The DNA codes small interfering RNA, micro-RNA, double-stranded RNA, small hairpin RNA or their precursors. The DNA further contains regulatory element, which permits an expression in a target cell. The mass ratio of the virus-like particle to RNA-interference-inducing molecule is 100:1 to 1:100, preferably 1:1 to 20:1. The virus-like particle contains the capsid protein VP-1 of the human polyoma JC virus. The virus-like particle is free of other components of the authentic virus. At least a capsid protein of the virus-like particle is modified. At least a capsid protein is chemically modified. At least a capsid protein of the virus-like particle is associated with at least a target cell specific group. The target cell specific group is a ligand, which can be bonded with receptors, which are present on the cell surfaces of the target cells. The ligand is transferrin and the receptor is transferrin receptor. The target cell specific group is associated over chemical compound groups to at least a capsid protein of the virus-like protein. The compound group is a cationic polymer. The cationic polymer is polyethylenimine. The capsid protein is a fusion protein. The fusion part is not interfered with the formation of the virus-like protein. The fusion part can be bound with receptors, which are present on the cell surfaces of a target cell. The virus-like protein consisting of a modified capsid protein exhibits a host spectrum, which is not corresponded to the host spectrum of the unmodified virus-like protein. The capsid protein of the virus-like protein is recombinantly produced. Preferred Method: The method of producing the composition, further comprises binding a target cell specific group, which can be bound with receptors on the surface of a target cell, to the virus-like protein. #CMT#EXAMPLE : #/CMT# The composition comprised of virus-like particle to RNA-interference-inducing molecule. The RNA-oligonucleotide was chemically synthesized. All small interfering RNA (siRNA) molecule contained 3'-dTdT-overhangs e.g. siLamA1 (target human Lamin A/C, modification 3'dTdT-overhangs). The VP-1 protein of the polyoma-JC-virus was expressed by means of a baculovirus system in insect cells.</p> |
