Lipid nanoparticle compositions for delivery of nucleic acids are described. In various embodiments the lipid nanoparticle contains an ionizable lipid of the Formula (I). Methods of using such lipid nanoparticle compositions to achieve targeted delivery of therapeutic cargo without the need for a targeting ligand are also provided.

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Amines and amine derivatives that improve the buffering range, and/or reduce the chelation and other negative interactions of the buffer and the system to be buffered. The reaction of amines or polyamines with various molecules to form polyamines with differing pKa's will extend the buffering range, derivatives that result in polyamines that have the same pKa yields a greater buffering capacity. Derivatives that result in zwitterionic buffers improve yield by allowing a greater range of stability.

Amines and amine derivatives that improve the buffering range, and/or reduce the chelation and other negative interactions of the buffer and the system to be buffered. The reaction of amines or polyamines with various molecules to form polyamines with differing pKa's will extend the buffering range, derivatives that result in polyamines that have the same pKa yields a greater buffering capacity. Derivatives that result in zwitterionic buffers improve yield by allowing a greater range of stability.

Amines and amine derivatives that improve the buffering range, and/or reduce the chelation and other negative interactions of the buffer and the system to be buffered. The reaction of amines or polyamines with various molecules to form polyamines with differing pKa's will extend the buffering range, derivatives that result in polyamines that have the same pKa yields a greater buffering capacity. Derivatives that result in zwitterionic buffers improve yield by allowing a greater range of stability.

Amines and amine derivatives that improve the buffering range, and/or reduce the chelation and other negative interactions of the buffer and the system to be buffered. The reaction of amines or polyamines with various molecules to form polyamines with differing pKa's will extend the buffering range, derivatives that result in polyamines that have the same pKa yields a greater buffering capacity. Derivatives that result in zwitterionic buffers improve yield by allowing a greater range of stability.

Amines and amine derivatives that improve the buffering range, and/or reduce the chelation and other negative interactions of the buffer and the system to be buffered. The reaction of amines or polyamines with various molecules to form polyamines with differing pKa's will extend the buffering range, derivatives that result in polyamines that have the same pKa yields a greater buffering capacity. Derivatives that result in zwitterionic buffers improve yield by allowing a greater range of stability.

This invention provides for a compound of formula (I):

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or a pharmaceutically acceptable salt thereof, wherein R.sup.1-R.sup.4, L and X are defined herein. The compounds of formula (I) and pharmaceutically acceptable salts thereof are cationic lipids useful in the delivery of biologically active agents to cells and tissues.

This invention provides for a compound of formula (I):

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or a pharmaceutically acceptable salt thereof, wherein R.sup.1-R.sup.4, L and X are defined herein. The compounds of formula (I) and pharmaceutically acceptable salts thereof are cationic lipids useful in the delivery of biologically active agents to cells and tissues.

A process of dissolving ##STR00001##
in a solvent to produce a first mixture. To the first mixture a reagent is added to produce a second mixture. A HRR is then added to the second mixture to produce a third mixture. The third mixture is then refluxed to produce ##STR00002##

A process of dissolving ##STR00001##
in a solvent to produce a first mixture. To the first mixture a reagent is added to produce a second mixture. A HRR is then added to the second mixture to produce a third mixture. The third mixture is then refluxed to produce ##STR00002##