Lipids for use in lipid nanoparticle formulations

A compound having a structure of Formula I:

• or a pharmaceutically acceptable salt, tautomer, prodrug or stereoisomer thereof, wherein:
• L1 and L2 are each independently —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—;
• G1 is C1-C2 alkylene, —(C═O)—, —O(C═O)—, —SC(═O)—, —NRaC(═O)— or a direct bond;
• G2 is —C(═O)—, —(C═O)O—, —C(═O)S—, —C(═O)NRa— or a direct bond;
• G3 is C1-C6 alkylene;
• Ra is H or C1-C12 alkyl;
• R1a and R1b are, at each occurrence, independently either:
• (a) H or C1-C12 alkyl;
• or (b) R1a is H or C1-C12 alkyl, and R1b together with the carbon atom to which it is bound to taken together with an adjacent R1b and the carbon atom to which it is bound to form a carbon-carbon double bond;
• R2a and R2b are, at each occurrence, independently either:
• (a) H or C1-C12 alkyl;
• or (b) R1a is H or C1-C12 alkyl, and R2b together with the carbon atom to which it is bound is taken together with an adjacent R2b and the carbon atom to which it is bound to form a carbon-carbon double bond;
• R3a and R3b are, at each occurrence, independently either (a):
• H or C1-C12 alkyl;
• or (b) R3a is H or C1-C12 alkyl, and R3b together with the carbon atom to which it is bound is taken together with an adjacent R3b and the carbon atom to which it is bound to form a carbon-carbon double bond;
• R4a and R4b are, at each occurrence, independently either:
• (a) H or C1-C12 alkyl;
• or (b) R4a is H or C1-C12 alkyl, and R4b together with the carbon atom to which it is bound is taken together with an adjacent R4b and the carbon atom to which it is bound to form a carbon-carbon double bond;
• R5 and R6 are each independently H or methyl;
• R7 is H or C1-C20 alkyl;
• R8 is OH, —N(R9)(C═O)R10, —(C═O)NR9R10, —NR9R10, —(C═O)OR11 or
• —O(C═O)R11, provided that G3 is C4-C6 alkylene when R8 is —NR9R10,
• R9 and R10 are each independently H or C1-C12 alkyl;
• R11 is aralkyl;
• a, b, c and d are each independently an integer from 1 to 24;
• and
• x is 0, 1 or 2,
• wherein each alkyl, alkylene and aralkyl is optionally substituted.