Conjugates for introducing nucleic acid into higher eucaryotic cells
AssigneesBoehringer Ingelheim International GmbH, Genentech, Inc., The University of North Carolina at Chapel Hill
InventorsDavid T. Curiel, Ping-chuan Hu, Max L. Birnstiel, Matthew Cotten, Ernst Wagner
Life of this patent
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Abstract
Conjugates in which a virus is bound via an antibody to a substance having an affinity for nucleic acid, for transporting gene constructs into higher eucaryotic cells. Complexes of the conjugates and nucleic acid are internalized in the cell, whilst the virus as part of the complex brings about the internalization and the release of the contents of the endosomes, in which the complexes are located after entering the cell. Pharmaceutical preparations in which the nucleic acid is a therapeutically active gene construct, particularly for use in gene therapy.
Claims15
An adenovirus conjugate which is capable of forming a complex with a nucleic acid and delivering said nucleic acid into the cytoplasm of a higher eukaryotic cell by endosomolysis, said adenovirus conjugate comprising an adenovirus capable of endosomolysis, which is bound to an antibody through a specific antigen/antibody bond wherein said antibody is covalently bound to a polycation having affinity for a nucleic acid, and wherein said conjugate is internalized into an endosome of a higher eukaryotic cell via receptor mediated endocytosis and said nucleic acid is released into the cytoplasm of the higher eukaryotic cell via endosomolysis which is mediated by the adenovirus.
A transfection kit, comprising a carrier means having in close confinement therein two or more container means, wherein a first container means contains a conjugate comprising a polycation having affinity for a nucleic acid bound to an antibody, and a second container means which contains an adenovirus to which the antibody of the first container means is capable of binding wherein said adenovirus
- (a) is capable of being internalized into an endosome of a higher eucaryotic cell when it is part of a complex comprising:
- (i) said polycation having affinity for a nucleic acid and
- (ii) a nucleic acid;
- and wherein said adenovirus
- (b) causes the release of the contents of the endosome of the higher eucaryotic cell into the cytoplasm of the higher eucaryotic cell by endosomolysis.
A transfection kit, comprising a carrier means having in close confinement therein one or more container means, wherein a container means contains a conjugate comprising a polycation having affinity for a nucleic acid which is bound via an antibody to an adenovirus, wherein said adenovirus
- (a) is capable of being internalized into an endosome of a higher eucaryotic cell when it is part of a complex comprising
- (i) said polycation having affinity for a nucleic acid and
- (ii) a nucleic acid;
- and wherein said adenovirus
- (b) causes release of the contents of the endosome of said higher eucaryotic cell into the cytoplasm of said higher eucaryotic cell by endosomolysis.
Dependencies are inferred from the claim text.