Nucleic acid delivery formulations
First Claim
1. An injectable aqueous formulation, comprising:
- a nucleic acid;
a first non-nucleic acid, water-soluble component; and
a second non-nucleic acid, water-soluble component, wherein the first and second components each include two or more reactive groups, the reactive groups of the first component being reactive with the reactive groups of the second component.
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Accused Products
Abstract
The invention is based on the discovery that injectable and nucleic acid-compatible polymeric compositions and formulations can be structurally designed to regulate nucleic acid activity or gene expression in vivo, for example, by controlling the bioavailability of the nucleic acid via modulation of the biodegradability and crosslink density of the network formed by the components of the formulation. The polymeric network encases the nucleic acid, not only controlling the release of the DNA, but also providing protection from degradation. The invention described herein improves upon prior modes of gene delivery, in that gene expression can be regulated by modulation of a polymeric network formed by combination of at least two water-soluble components capable of reacting with one another. The nucleic acid of interest is incorporated into the network to be released in a sustained manner to achieve level and duration of activity or expression needed.
43 Citations
88 Claims
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1. An injectable aqueous formulation, comprising:
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a nucleic acid;
a first non-nucleic acid, water-soluble component; and
a second non-nucleic acid, water-soluble component, wherein the first and second components each include two or more reactive groups, the reactive groups of the first component being reactive with the reactive groups of the second component. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63)
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64. A method of making a dried nucleic acid formulation comprising:
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(a) preparing a mixture by mixing in an aqueous solution (i) a nucleic acid, (ii) a first non-nucleic acid, water-soluble component, (iii) a second non-nucleic acid, water-soluble component, and (iv) a third non-nucleic acid, water-soluble component, wherein the first and second components each include two or more reactive groups, the reactive groups of the first component being reactive with the reactive groups of the second component at a pH greater than 7.0, and wherein the aqueous solution has a pH and temperature that prevents the first and second components from reacting to form a cross-linked network; and
(b) drying the mixture to thereby create a dried nucleic acid formulation. - View Dependent Claims (65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77)
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78. A dried formulation comprising:
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(a) a nucleic acid;
(b) a first non-nucleic acid, water-soluble component;
(c) a second non-nucleic acid, water-soluble component; and
(d) a third non-nucleic acid, water-soluble component, wherein the first and second components each include two or more reactive groups, the reactive groups of the first component being reactive with the reactive groups of the second component, wherein the first and second components are in an unreacted state, and wherein the nucleic acid and the three components are not in solution. - View Dependent Claims (79, 80, 81, 82, 83, 84, 85)
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86. A method of delivering a particle to an individual, the method comprising:
administering to the individual a formulation comprising said particle;
a first, non-nucleic acid, water soluble component; and
a second, non-nucleic acid, water soluble component, wherein the first and second components each include two or more reactive groups, the reactive groups of the first component being reactive with the reactive groups of the second component.- View Dependent Claims (87, 88)
Specification