Compositions and methods for targeted systemic delivery to cells

A composition formulated for systemic (e.g., intravenous) administration, the composition comprising a therapeutic agent assembled with a lipid composition that comprises:

• (i) an ionizable cationic lipid;
• (ii) a polymer-conjugated lipid;
• and
• (iii) a selective organ targeting (SORT) lipid has the structure of Formula (S-III), or a pharmaceutically acceptable salt, stereoisomer, tautomer thereof:
• wherein:
• R1 and R2 are each independently alkyl(C8-C24), alkenyl(C8-C24), or a substituted version of either group;
• R3, R3′, and R3″ are each independently alkyl(C≤6) or substituted alkyl(C≤6);
• and
• X− is a monovalent anion.