Compositions and methods for delivery of RNA
AssigneeRejuvenation Technologies, Inc.
InventorsJohn Ramunas, Glenn Jeremy Markov, William Gillis Olsen, Kyle Daniel Brewer
Life of this patent
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Abstract
The lipid nanoparticle compositions provided herein preferentially deliver and/or transfect the lung. Also provided herein are therapeutic polynucleotides, e.g. TERT mRNA, which may be delivered with the LNP formulations for the treatment of lung disease and fibrosis.
Claims32
A method of delivering a polynucleotide to the lung of a subject, comprising administering to a lung tissue cell a pharmaceutical lipid nanoparticle (LNP) composition comprising RNA, the LNP comprising a total lipid amount including:
- (a) a structural lipid at a molar percentage of between at or about 0% to 1% of the total lipid in the LNP;
- (b) an insulator lipid at a molar percentage of between at or about 0.1% to 6% of the total lipid in the LNP;
- (c) a cholesterol lipid at a molar percentage of between at or about 0% to 40% of the total lipid in the LNP;
- (d) an ionizable lipid comprising SS-OP or an SS-OP analog, at a molar percentage of between at or about 30% to 60% of the total lipid in the LNP;
- and
- (e) a permanently cationic lipid at a molar percentage of between at or about 20% to 80% of the total lipid in the LNP;
- wherein the liposomal pKa of the LNP is between at or about 5.5 to 7.2;
- and
- wherein the RNA is encapsulated in the LNP and encodes telomerase reverse transcriptase (TERT) mRNA having one or more modified nucleotides, wherein the LNP preferentially delivers to the lung compared to liver or transfects lung tissue cells compared to liver tissue cells, and wherein telomeres are extended within the lung tissue cells.
A method of treating a lung disease and/or lung fibrosis in a subject in need thereof, comprising administering an effective amount of:
- a composition comprising a lipid nanoparticle (LNP) wherein the LNP comprising a total lipid amount including:
- (a) an insulator lipid at a molar percentage of between at or about 0.1% to 26% of the total lipid in the LNP;
- (b) a cholesterol lipid at a molar percentage of between at or about 30% to 40% of the total lipid in the LNP;
- (c) an ionizable lipid comprising SS-OP or an SS-OP analog, at a molar percentage of between at or about 30% to 50% of the total lipid in the LNP;
- and
- (d) a permanently cationic lipid at a molar percentage of between at or about 15% to 25% of the total lipid in the LNP;
- wherein the liposomal pKa of the LNP is between at or about 5.5 to 7.2;
- wherein the composition is substantially free of structural lipids;
- and
- wherein the RNA is encapsulated in the LNP and encodes telomerase reverse transcriptase (TERT) mRNA having one or more modified nucleotides, wherein the LNP preferentially delivers to the lung compared to liver or transfects lung tissue cells compared to liver tissue cells, and wherein telomeres are extended within the lung tissue cells.
A composition, comprising a lipid nanoparticle (LNP) comprising a total lipid amount including:
- (a) an insulator lipid at a molar percentage of between at or about 0.1% to 2% of the total lipid in the LNP;
- (b) a cholesterol lipid at a molar percentage of between at or about 30% to 40% of the total lipid in the LNP;
- (c) an ionizable lipid comprising SS-OP or an SS-OP analog, at a molar percentage of between at or about 30% to 60% of the total lipid in the LNP;
- and
- (d) a permanently cationic lipid at a molar percentage of between at or about 15% to 25% of the total lipid in the LNP;
- wherein the liposomal pKa of the LNP is between at or about 5.5 to 7.2;
- wherein the composition is substantially free of structural lipids;
- and
- wherein the RNA is encapsulated in the LNP and encodes telomerase reverse transcriptase (TERT) mRNA having one or more modified nucleotides.
Dependencies are inferred from the claim text.