Multifunctional molecular complexes for gene transfer to cells
AssigneeWyeth
InventorRaymond Boutin
Life of this patent
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Abstract
A multifunctional molecular complex for the transfer of a nucleic acid composition to a target cell is provided. The complex is comprised of A) said nucleic acid composition and B) a transfer moiety comprising 1) one or more cationic polyamines bound to said nucleic acid compositions, 2) one or more endosome membrane disrupting components attached to at least one nitrogen of the polyamine and 3) one or more receptor specific binding components.
Claims20
A method for the transfer of a nucleic acid composition to cells, comprising the step of introducing a multifunctional molecular complex into cells,
- wherein said multifunctional molecular complex comprises:
- A) a nucleic acid composition;
- and
- B) a transfer moiety comprising
- (i) one or more cationic polyamine components, wherein each cationic polyamine is non-covalently bound to said nucleic acid composition and comprises from three to twelve nitrogen atoms;
- and
- (ii) 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, said one or more endosome membrane disruption promoting components independently selected from (a) at least one lipophilic long chain alkyl group or (b) a fusogenic peptide, cholic acid or cholesteryl group or a derivative thereof;
- wherein said multifunctional molecular complex transfers said nucleic acid composition to said cells.
A method of immunization against a pathogen comprising the step of introducing a multifunctional molecular complex;
- wherein said multifunctional molecular complex comprises:
- A) a nucleic acid composition;
- and
- B) a transfer moiety comprising
- (i) one or more cationic polyamine components, wherein each cationic polyamine is non-covalently bound to said nucleic acid composition and comprises from three to twelve nitrogen atoms;
- and
- (ii) 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, said one or more endosome membrane disruption promoting components independently selected from (a) at least one lipophilic long chain alkyl group or (b) a fusogenic peptide, cholic acid or cholesteryl group or a derivative thereof;
- wherein said multifunctional molecular complex transfers said nucleic acid composition to said cells,
- wherein said nucleic acid molecule comprises a nucleotide sequence that encodes a peptide which comprises at least an epitope identical to, or substantially similar to an epitope displayed on said pathogen as antigen and wherein said nucleotide sequence is operatively linked to regulatory sequences;
- and wherein said nucleic acid molecule is capable of being expressed in the cells.
A method for delivering a nucleic acid molecule to a targeted population of cells of an individual, said method comprising the step of delivering to the individual a multifunctional molecular complex comprising:
- A) a nucleic acid molecule;
- and
- B) a transfer moiety comprising one or more cationic polyamine components, wherein each cationic polyamine is non-covalently bound to said nucleic acid molecule and each independently comprises a cationic polyamine of the formula (1):
- NR(R3)—[—(CR1R2)m—N(R3)—]n—(CR1R2)m—NR(R3) (1)
- wherein:
- R, R1 and R2 are each independently selected from the group consisting of hydrogen and C1-6 alkyl;
- m in each occurrence is independently selected from the integers 2 through 5 inclusive,
- n is selected from the integers 1 through 10 inclusive;
- R3 is independently selected from the group consisting of hydrogen;
- C1-6 alkyl, and an endosome membrane disruption promoting component, or NR(R3) is guanidino;
- wherein said transfer moiety comprises at least one endosome membrane disruption promoting component attached to at least one nitrogen atom of at least one of said cationic polyamine components;
- wherein said transfer moiety comprises at least one receptor specific binding component attached either (i) to a further nitrogen atom of at least one of said cationic polyamine components to which said one or more endosome membrane disruption promoting components is attached, or (ii) to a nitrogen atom of at least one further polyamine component which does not have attached thereto any endosome membrane disruption promoting component,
- wherein said receptor specific binding component which is a ligand for natural receptors of said target cells.
Dependencies are inferred from the claim text.