Poly(histidine)-based micelles for complexation and delivery of proteins and nucleic acids
Inventors
Ghoroghchian, Paiman Peter • ROMERO URIBE, Gabriela • Ostertag, Eric
Assignees
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Publication Number
US-11213594-B2
Publication Date
2022-01-04
Expiration Date
Abstract
Disclosed are compositions for delivering gene editing molecules to a cell. Exemplary compositions comprise a micelle assembled from a plurality of triblock copolymers, wherein each triblock copolymer having at least one hydrophobic block, at least one hydrophilic block, and at least one poly(L-histidine) block, wherein: the at least one poly(L-histidine) block complexes with the at least one gene editing molecule; and the at least one poly(L-histidine) block is capable of a pH dependent release of the at least one gene editing molecule.
Core Innovation
The invention provides a composition for delivering at least one gene editing molecule to a cell using micelles assembled from a plurality of triblock copolymers. Each triblock copolymer has at least one hydrophobic block, at least one hydrophilic block, and at least one poly(L-histidine) block. The micelles are formed such that the at least one poly(L-histidine) block complexes with the at least one gene editing molecule and is capable of pH dependent release of the at least one gene editing molecule.
In the micelle architecture, the at least one hydrophilic block comprises poly(ethylene oxide) and the at least one hydrophobic block comprises poly(lactic acid). The gene editing molecule comprises one or more of a nucleic acid encoding for a protein, where the protein is selected from transposase, nuclease, and integrase, or alternatively comprises one or more of a protein selected from transposase, nuclease, and integrase. The composition uses a specified molar ratio of triblock copolymers to the at least one gene editing molecule.
The invention addresses delivering gene editing molecules to cells, including embodiments where the gene editing molecule encodes a protein selected from transposase, nuclease, and integrase. The micelles are configured to complex the gene editing molecule via poly(L-histidine) and to provide pH dependent release. Gene editing molecule options in related embodiments include nucleic acid and/or transposable elements and corresponding transposase proteins, with specific examples including piggyBac, Sleeping Beauty, and LINE-1 (L1).
Claims Coverage
The provided claim set includes two independent claims with core inventive features centered on poly(L-histidine)-containing triblock copolymer micelles that complex gene editing molecules and provide pH dependent release, with specific hydrophilic (poly(ethylene oxide)) and hydrophobic (poly(lactic acid)) blocks and defined copolymer-to-gene editing molar ratios.
Poly(L-histidine) triblock copolymer micelle complexing and pH dependent release
A micelle assembled from a plurality of triblock copolymers, each having at least one hydrophobic block, at least one hydrophilic block, and at least one poly(L-histidine) block, wherein the at least one poly(L-histidine) block complexes with the at least one gene editing molecule and is capable of a pH dependent release of the at least one gene editing molecule.
Poly(ethylene oxide) hydrophilic block and poly(lactic acid) hydrophobic block
The at least one hydrophilic block comprises poly(ethylene oxide) and the at least one hydrophobic block comprises poly(lactic acid).
Gene editing molecule encoding transposase, nuclease, or integrase
The at least one gene editing molecule comprises one or more of a nucleic acid encoding for a protein, wherein the protein is selected from the group consisting of a transposase, a nuclease and an integrase (or comprises one or more of a protein selected from the group consisting of a transposase, a nuclease and an integrase).
Specified molar ratio of triblock copolymers to gene editing molecule
The molar ratio of triblock copolymers to the at least one gene editing molecule is about 20:1 (or about 2:3 in the alternative independent claim).
Kit with pharmaceutical composition and administration implement for multiple routes
A kit including a pharmaceutical composition of the micelle composition and an administration implement configured to administer the pharmaceutical composition by multiple administration routes.
Across the independent claims, the invention is directed to triblock copolymer micelles containing poly(L-histidine) that complex gene editing molecules and provide pH dependent release, using poly(ethylene oxide) as hydrophilic and poly(lactic acid) as hydrophobic blocks, with gene editing proteins selected from transposase, nuclease, and integrase and defined triblock copolymer-to-gene editing molar ratios.
Stated Advantages
Documented Applications
No documented applications found
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