Transfection reagents for delivery of nucleic acids
Inventors
Uludag, Hasan • KC, Remant Badahur • VALENCIA-SERNA, Juliana
Assignees
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Publication Number
US-11964057-B2
Publication Date
2024-04-23
Expiration Date
Abstract
Polymeric transfection reagents for delivery of nucleic acids to cells, pharmaceutical compositions comprising same, and methods of preparing and using same are provided. A compound comprises polyethylenimine, a lipid selected from cholesterol, lauric acid, palmitic acid, or stearic acid, and optionally, a histidine. A nanoparticle comprises the compound complexed to a nucleic acid. A composition or pharmaceutical composition comprises the nanoparticle and a pharmaceutically acceptable carrier, anti-fouling agent, targeting ligand, or combinations thereof. A method of treating, preventing, or ameliorating a disease in a subject comprises administering to the subject an effective amount of the nanoparticle or the composition or pharmaceutical composition.
Core Innovation
The invention relates to a compound comprising a polymer and a lipid covalently linked via N-acylation. The polymer is polyethylenimine having a molecular weight ranging from 0.6 kDa to 2.0 kDa, and the lipid is cholesterol or a derivative thereof, or lauric acid. The compound is capable of delivering ribonucleic acid.
The invention further provides nanoparticles comprising the compound complexed to a ribonucleic acid, or compositions comprising the compound or the nanoparticle and pharmaceutically acceptable carrier. The compositions can further include a targeting ligand and an anti-fouling agent.
In particular embodiments, the compound is defined by repeating units in polyethylenimine and a linker R having a spacer and a cleavable group. The invention positions these structures within delivery of ribonucleic acid in blood cancer treatment contexts.
Claims Coverage
The independent claims are directed to a polyethylenimine-lipid conjugate and a method of treating, preventing, or ameliorating blood cancer using the compound or related nanoparticle/composition. Across the independent claims, the main inventive elements are the N-acylation-linked polyethylenimine-lipid conjugate, the ribonucleic-acid delivery capability, and optional formulation features such as nanoparticle complexation plus targeting ligand and anti-fouling agent.
N-acylation-linked polyethylenimine-lipid conjugate
A compound comprising a polymer and a lipid covalently linked via N-acylation, wherein the polymer is polyethylenimine having a molecular weight ranging from 0.6 kDa to 2.0 kDa, and wherein the lipid is cholesterol or a derivative thereof, or lauric acid.
Blood cancer treatment using a ribonucleic-acid-delivering compound
A method of treating, preventing, or ameliorating blood cancer in a subject, comprising administering an effective amount of a compound capable of delivering a ribonucleic acid, or a nanoparticle comprising the compound complexed to a ribonucleic acid, or a composition comprising the compound or the nanoparticle and a pharmaceutically acceptable carrier, a targeting ligand, an anti-fouling agent, or combination thereof.
Defined polyethylenimine repeating-unit compound
A compound having the formula (I), wherein x, y and z are repeating units in polyethylenimine, with x is 7 to 22 repeating units, y is 14 to 44 repeating units, and z is 1 to 5 repeating units, and wherein the compound is capable of delivering a ribonucleic acid.
The claim set centers on polyethylenimine covalently linked to cholesterol or derivatives thereof, or lauric acid, via N-acylation, with the compound capable of delivering ribonucleic acid. Dependent limitations further constrain structural parameters, including linker spacer and cleavable groups and polyethylenimine repeating-unit ranges, and support blood-cancer treatment use via nanoparticle complexation and optional targeting ligand and anti-fouling agent components.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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