Lipids and lipid nanoparticle formulations

A compound of Formula I-1:

• wherein:
• L1 is C1-10 alkylene or C2-10 heteroalkylene;
• wherein the C2-10 heteroalkylene is optionally substituted with R6;
• L2 is C1-10 alkylene or C2-10 heteroalkylene;
• wherein the C2-10 heteroalkylene is optionally substituted with R6;
• X is —CH2—, —NR3—, —N(R3)2+—, —O—, —O—CH2CH2—O—, or —NR3—(CH2)m—NR3—;
• m is an integer from 1 to 6;
• R1, R2, and R3 are each independently hydrogen, C1-20 alkyl, C2-20 alkenyl, C2-20 alkynyl, C2-20 heteroalkyl,
• wherein the C1-20 alkyl, C2-20 alkenyl, C2-20 alkynyl, or C2-20 heteroalkyl is independently optionally substituted with one to five halo, cyano, —OR4, —SR4, —NR42, —N(R4)3+, oxo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 haloalkyl;
• each Ra is independently hydrogen, C1-12 alkyl, or —C(O)—C1-12 alkyl;
• each R4 is independently hydrogen, C1-12 alkyl, C2-12 alkenyl, or C2-12 alkynyl;
• wherein each C1-12 alkyl, C2-12 alkenyl, or C2-12 alkynyl is independently optionally substituted with one to five halo, cyano, —OH, —SR5, —NR52, —N(R5)3+, or oxo;
• each R5 is independently hydrogen, C1-12 alkyl, C2-12 alkenyl, or C2-12 alkynyl;
• wherein each C1-12 alkyl, C2-12 alkenyl, or C2-12 alkynyl is independently optionally substituted with one to five halo, cyano, —OH, —SH, —NH2, —NH(C1-6 alkyl), —N(C1-6 alkyl)2, —N(C1-6 alkyl)3+, or oxo;
• each R6 is independently
• each L is independently C1-10 alkylene or C3-10 heteroalkylene;
• each Y is independently —O— or —NR7—;
• each R7 is independently hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 haloalkyl;
• wherein each C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 haloalkyl is independently optionally substituted with one to five halo, cyano, —OH, —NH2, —NH(C1-6 alkyl), —N(C1-6 alkyl)2, —N(C1-6 alkyl)3+, oxo, C1-6 alkoxy, or C1-6 haloalkoxy;
• each n is independently an integer from 1-20;
• each R is independently hydrogen, —Z—C1-20 alkyl, —Z—C2-20 alkenyl, —Z—C2-20 alkynyl, —Z-heterocyclyl, —Z1—C1-6 alkylene-Z—C1-20 alkyl, —Z1—C1-6 alkylene-Z—C2-20 alkenyl, —Z1—C1-6 alkylene-Z—C2-20 alkynyl, —Z1—C1-6 alkylene-Z-heterocyclyl, —Z1—C2-6 alkenyl-Z—C1-20 alkyl, —Z1—C2-6 alkenyl-Z—C2-20 alkenyl, —Z1—C2-6 alkenyl-Z—C2-20 alkynyl, —Z1—C2-6 alkynyl-Z—C1-20 alkyl, —Z1—C2-6 alkynyl-Z—C2-20 alkenyl, or —Z1—C2-6 alkynyl-Z—C2-20 alkynyl;
• each Z is independently a bond, —O—, —NR4—, —S—, —S—S—, —C(O)—, —C(O)O—, —OC(O)—, —C(O)NR4—, —S(O)—, —S(O)2—, —NR4C(O)—, —NR4C(O)O—, —NR4C(O)NR4—, —NR4S(O)—, or —S(O)2NR4—;
• and
• each Z1 is independently —O—, —NR4—, —S—, —S—S—, —C(O)—, —C(O)O—, —C(O)NR4—, —S(O)—, —S(O)2—, —NR4C(O)—, —NR4C(O)O—, —NR4C(O)NR4—, —NR4S(O)—, or —S(O)2NR4—;
• provided that each
• moiety comprises at least 6 linear atoms.