Complexes comprising a nucleic acid bound to a cationic polyamin

Chemistry: molecular biology and microbiology – Vector – per se

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4351723, 935 52, C12N 500, C12N15000

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058375333

ABSTRACT:
A multifunctional molecular complex for the transfer of a nucleic acid composition to a target cell is provided which comprises in any functional combination: A) said nucleic acid composition; and B) a transfer moiety comprising 1) one or more cationic polyamine components bound to said nucleic acid composition, each comprising from three to twelve nitrogen atoms; 2) one or more endosome membrane disruption promoting components attached to at least one nitrogen atom of at least one of said polyamine components, through an alkyl, carboxamide, carbamate, thiocarbamate, or carbamoyl bridging group, comprising a) at least one lipophilic long chain alkyl group, b) a fusogenic peptide comprising spike glycoproteins of enveloped animal viruses, or c) cholic acid or cholesteryl or derivatives; and optionally 3) one or more receptor specific binding components which are ligands for natural receptors of said target cell, attached through an alkyl, carboxamide, carbamate, thiocarbamate, or carbamoyl bridging group to either i) a further nitrogen atom of at least one of said polyamine components to which said one or more endosome membrane disruption promoting components is attached, or ii) a nitrogen atom of at least one further polyamine component which does not have attached thereto any endosome membrane disruption promoting component. Also provided are the transfer moiety alone, or in combination with the nucleic acid composition as a self-assembling combination, and the use of these compositions in methods for transfering nucleic acid compositions to cells or to cells of individuals, for immunizing individuals against a pathogen or disease, and for treating an individual with a disease.

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