Lipid nanoparticle formulations

A lipid nanoparticle comprising:

• i) from 47 to 48 mol percent of a cationic lipid;
• ii) a neutral lipid;
• iii) a steroid;
• iv) a polymer conjugated lipid;
• and
• v) a therapeutic agent, or a pharmaceutically acceptable salt thereof, encapsulated within or associated with the lipid nanoparticle, wherein the cationic lipid has a structure of Formula III:
• or a pharmaceutically acceptable salt or stereoisomer thereof, wherein:
• one of L1 or L2 is —O(C═O)—, —(C═O)O—, —C(═O)—, —O—, —S(O)x—, —S—S—, —C(═O)S—, SC(═O)—, —NRaC(═O)—, —C(═O) NRa—NRaC(═O) NRa—, —OC(═O) NRa— or —NRaC(═O)O—, and the other of L1 or L2 is —O(C═O)—, —(C═O)O—, —C(═O)—, —O—, —S(O)x—, —S—S—, —C(═O)S—, SC(═O)—, —NRaC(═O)—, —C(═O) NRa, —NRaC(═O) NRa—, —OC(═O) NRa— or —NRaC(═O)O— or a direct bond;
• G1 and G2 are each independently unsubstituted C1-C12 alkylene or C1-C12 alkenylene;
• G3 is C1-C24 alkylene, C1-C24 alkenylene, C3-C8 cycloalkylene, C3-C8 cycloalkenylene;
• Ra is H or C1-C12 alkyl;
• R1 and R2 are each independently C6-C24 alkyl or C6-C24 alkenyl;
• R3 is H, OR5, CN, —C(═O)OR4, —OC(═O)R4 or —NRaC(═O)R4;
• R4 is C1-C12 alkyl;
• R5 is H or C1-C6 alkyl;
• and
• x is 0, 1 or 2.