Compositions and methods for polynucleotide delivery
AssigneeNovartis Vaccines and Diagnostics, Inc.
InventorsRonald Zuckermann, Nathalie Dubois-Stringfellow, Varavani Dwarki, Michael Innis, John Murphy, Fred Cohen, Tetsuo Uno
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Abstract
This invention relates compositions and methods for increasing the uptake of polynucleotides into cells. Specifically, the invention relates to vectors, targeting ligands, and polycationic agents. The polycationic agents are capable of (1) increasing the frequency of uptake of polynucleotides into a cell, (2) condensing polynucleotides; and (3) inhibiting serum and/or nuclease degradation of polynucleotides.
Claims29
A polycationic agent having the following formula:
- wherein
- n is an integer from 10 to 100;
- R1, R2, and R3 for each monomer,
- are independently selected from moieties having a molecular weight from 1 to 200 daltons;
- Ta and Tc are terminating groups;
- R1 is not hydrogen for at least one monomer;
- wherein said polycationic agent comprises at least 25% positively charged monomers, excluding the terminal groups, and
- wherein said polycationic agent exhibits a net positive electrical charge at a physiological pH.
A composition comprising:
- (i) a lipoprotein;
- (ii) a polynucleotide binding molecule;
- and
- (iii) a polynucleotide,
- wherein said composition is capable of increasing the frequency of polynucleotide uptake into a cell.
A pharmaceutical composition comprising
- (a) a therapeutically effective amount of a polynucleotide;
- (b) a polynucleotide binding molecule in an amount effective to neutralize the negative charge of said polynucleotide;
- and
- (c) a therapeutically effective amount of lipoprotein.
The pharmaceutical composition of claim 26, wherein said polynucleotide is a polycationic agent.
A method of producing a composition for facilitating entry of a polynucleotide into a cell said method comprising:
- (i) providing a polynucleotide
- (ii) providing a polynucleotide binding molecule in an amount effective to neutralize said polynucleotide;
- (ii) contacting said polynucleotide with said polynucleotide binding molecule to form a complex;
- (iii) providing a lipoprotein;
- then
- (iv) contacting the complex with said lipoprotein.
A method of increasing the frequency of polynucleotide uptake into a cell said method comprising
- (i) providing a composition that comprises
- (a) a therapeutically effective amount of a polynucleotide;
- (b) a polynucleotide binding molecule in an amount effective to neutralize said polynucleotide;
- and
- (c) an effective amount lipoprotein;
- then
- (ii) contacting said composition to said cell.
Dependencies are inferred from the claim text.