Poly(histidine)-based micelles for complexation and delivery of proteins and nucleic acids
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.
1. A composition for delivering at least one gene editing molecule to a cell, the composition comprising:
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;
the at least one poly(L-histidine) block is capable of a pH dependent release of the at least one gene editing molecule;
the at least one hydrophilic block comprises poly(ethylene oxide) and the at least one hydrophobic block comprises poly(lactic acid); and
wherein 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;
wherein the molar ratio of triblock copolymers to the at least one gene editing molecule is about 20:1.
2. The composition of claim 1 , wherein the nuclease is selected from the group comprising:
a CRISPR associated protein 9 (Cas9);
a type IIS restriction enzyme;
a transcription activator-like effector nuclease (TALEN); and
a zinc finger nuclease (ZFN).
3. The composition of claim 1 , wherein the at least one gene editing molecule further comprises one or more transposable elements.
4. The composition of claim 3 , wherein the one or more transposable elements comprise a piggyBac transposon, a Sleeping Beauty transposon or a LINE-1 (L1) transposon.
5. The composition of claim 1 , wherein the protein is a transposase.
6. A kit, comprising:
a pharmaceutical composition comprising the composition of claim 1 ; and
an implement for administering the pharmaceutical composition intravenously, via inhalation, topically, per rectum, per the vagina, transdermally, subcutaneously, intraperitoneally, intrathecally, intramuscularly or orally.
7. A composition for delivering at least one gene editing molecule to a cell, the composition comprising:
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;
the at least one poly(L-histidine) block is capable of a pH dependent release of the at least one gene editing molecule;
the at least one hydrophilic block comprises poly(ethylene oxide) and the at least one hydrophobic block comprises poly(lactic acid); and
wherein the at least one gene editing molecule comprises one or more of a protein, wherein the protein is selected from the group consisting of a transposase, a nuclease and an integrase;
wherein the molar ratio of triblock copolymers to the at least one gene editing molecule is about 2:3.
8. The composition of claim 7 , wherein the nuclease is selected from the group comprising:
a CRISPR associated protein 9 (Cas9);
a type IIS restriction enzyme;
a transcription activator-like effector nuclease (TALEN); and
a zinc finger nuclease (ZFN).
9. The composition of claim 7 , wherein the at least one gene editing molecule further comprises one or more transposable elements.
10. The composition of claim 9 , wherein the one or more transposable elements comprise a piggyBac transposon, a Sleeping Beauty transposon or a LINE- 1 (L 1 ) transposon.
11. The composition of claim 7 , wherein the protein is a transposase.
12. A kit, comprising:
a pharmaceutical composition comprising the composition of claim 7 ; and
an implement for administering the pharmaceutical composition intravenously, via inhalation, topically, per rectum, per the vagina, transdermally, subcutaneously, intraperitoneally, intrathecally, intramuscularly or orally.