NANOMATERIALS COMPRISING TRIOLS

1 . A method administering a therapeutic and/or prophylactic agent to a subject, the method comprising administering a lipid nanoparticle (LNP) preparation to the subject,

wherein the LNP preparation comprises:

a therapeutic and/or prophylactic agent comprising one or more nucleic acids;

an ionizable lipid, or a pharmaceutically acceptable salt thereof;

a phospholipid; and

a cholesterol; and

wherein the ionizable lipid is a compound of Formula IX-B-i:

or a pharmaceutically acceptable salt thereof, wherein:

each L 2 and L 2′ is independently a bivalent saturated, straight, or branched C 1-12 hydrocarbon chain;

R 1 is optionally substituted C 1-20 aliphatic;

each R 1′ is independently optionally substituted C 1-20 aliphatic;

Y 2 is a bivalent saturated, straight, or branched C 1-6 hydrocarbon chain;

Y 3 is optionally substituted C 1-20 aliphatic; and

—X 2 —X 3 is

 and

wherein the one or more nucleic acids is or comprises an mRNA.

2 . The method of claim 1 , wherein L 2 is a bivalent saturated, straight, or branched C 4-8 hydrocarbon chain and/or L 2′ is a bivalent saturated, straight, or branched C 1-6 hydrocarbon chain.

3 . The method of claim 2 , wherein

L 2 is —(CH 2 ) 6 — or —(CH 2 ) 7 — and L 2′ is —(CH 2 ) 2 —;

or

L 2 is —(CH 2 ) 4 — or —(CH 2 ) 5 — and L 2′ is —(CH 2 ) 2 —.

4 . The method of claim 1 , wherein R 1 is optionally substituted C 12-20 aliphatic and/or each R 1′ is independently optionally substituted C 7-9 aliphatic.

5 . The method of claim 1 , wherein R 1 is

and/or

each R 1′ is independently or

6 . The method of claim 1 , wherein L 2 is —(CH 2 ) 6 — and R 1 is

7 . The method of claim 1 , wherein Y 2 is —CH 2 — or —(CH 2 ) 2 — and/or Y 3 is optionally substituted C 4-8 aliphatic.

8 . The method of claim 1 , wherein the ionizable lipid is selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.

9 . A method of producing a polypeptide of interest in a mammalian cell, the method comprising contacting the cell with a lipid nanoparticle (LNP) preparation to a subject,

wherein the LNP preparation comprises:

a therapeutic and/or prophylactic agent comprising one or more nucleic acids;

an ionizable lipid, or a pharmaceutically acceptable salt thereof;

a phospholipid; and

a cholesterol; and

wherein the ionizable lipid is a compound of Formula IX-B-i:

or a pharmaceutically acceptable salt thereof, wherein:

each L 2 and L 2′ is independently a bivalent saturated, straight, or branched C 1-12 hydrocarbon chain;

R 1 is optionally substituted C 1-20 aliphatic;

each R 1′ is independently optionally substituted C 1-20 aliphatic;

Y 2 is a bivalent saturated, straight, or branched C 1-6 hydrocarbon chain;

Y 3 is optionally substituted C 1-20 aliphatic; and

—X 2 —X 3 is

 and

wherein the one or more nucleic acids is or comprises an mRNA, and wherein the mRNA encodes the polypeptide of interest, whereby the mRNA is capable of being translated in the cell to produce the polypeptide of interest.

10 . The method of claim 9 , wherein L 2 is a bivalent saturated, straight, or branched C 4-8 hydrocarbon chain and/or L 2′ is a bivalent saturated, straight, or branched C 1-6 hydrocarbon chain.

11 . The method of claim 10 , wherein

L 2 is —(CH 2 ) 6 — or —(CH 2 ) 7 — and L 2′ is —(CH 2 ) 2 —;

or

L 2 is —(CH 2 ) 4 — or —(CH 2 ) 5 — and L 2′ is —(CH 2 ) 2 —.

12 . The method of claim 9 , wherein R 1 is optionally substituted C 12-20 aliphatic and/or each R 1′ is independently optionally substituted C 7-9 aliphatic.

13 . The method of claim 9 , wherein R 1 is

and/or

each R 1′ is independently or

14 . The method of claim 9 , wherein L 2 is —(CH 2 ) 6 — and R 1 is

15 . The method of claim 9 , wherein Y 2 is —CH 2 — or —(CH 2 ) 2 — and/or Y 3 is optionally substituted C 4-8 aliphatic.

16 . The method of claim 9 , wherein the ionizable lipid is selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.

17 . A method of base editing a genome of a cell in a subject, the method comprising administering to the subject a composition comprising a lipid nanoparticle (LNP) preparation,

wherein the LNP preparation comprises:

a therapeutic and/or prophylactic agent comprising one or more nucleic acids;

an ionizable lipid, or a pharmaceutically acceptable salt thereof;

a phospholipid; and

a cholesterol; and

wherein the ionizable lipid is a compound of Formula IX-B-i:

or a pharmaceutically acceptable salt thereof, wherein:

each L 2 and L 2′ is independently a bivalent saturated, straight, or branched C 1-12 hydrocarbon chain;

R 1 is optionally substituted C 1-20 aliphatic;

each R 1′ is independently optionally substituted C 1-20 aliphatic;

Y 2 is a bivalent saturated, straight, or branched C 1-6 hydrocarbon chain;

Y 3 is optionally substituted C 1-20 aliphatic; and

—X 2 —X 3 is

 and

wherein the one or more nucleic acids comprises an mRNA encoding a base editor and a chemically modified sgRNA.

18 . The method of claim 17 , wherein L 2 is a bivalent saturated, straight, or branched C 4-8 hydrocarbon chain and/or L 2′ is a bivalent saturated, straight, or branched C 1-6 hydrocarbon chain.

19 . The method of claim 18 , wherein

L 2 is —(CH 2 ) 6 — or —(CH 2 ) 7 — and L 2′ is —(CH 2 ) 2 —;

or

L 2 is —(CH 2 ) 4 — or —(CH 2 ) 5 — and L 2′ is —(CH 2 ) 2 —.

20 . The method of claim 17 , wherein R 1 is optionally substituted C 12-20 aliphatic and/or each R 1′ is independently optionally substituted C 7-9 aliphatic.

21 . The method of claim 17 , wherein R 1 is

and/or

each R 1′ is independently or

22 . The method of claim 17 , wherein L 2 is —(CH 2 ) 6 — and R 1 is

23 . The method of claim 17 , wherein Y 2 is —CH 2 — or —(CH 2 ) 2 — and/or Y 3 is optionally substituted C 4-8 aliphatic.

24 . The method of claim 17 , wherein the ionizable lipid is selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.