Compositions and methods for capping rnas
AssigneeVerve Therapeutics, Inc.
InventorsChristopher Cheng, Kallanthottathil Rajeev, Caroline Reiss, Kui Wang, Jay Leipheimer
Life of this patent
Estimating the term…
Abstract
Provided herein are compositions and methods for preparation of 5′ end region-modified mRNAs. In particular, the instant disclosure relates to novel mRNA 5′ end region motifs and sequence initiators therefore together with assays that are capable of measuring the aspects of the functionality of those motifs and sequence initiators. Further provided herein are compositions and methods of treating conditions related to coronary disease.
Claims42
An in vitro-transcribed (IVT) mRNA sequence initiator comprising a compound of Formula (I) or a salt or solvate thereof:
- wherein
- B1 is
- each B2, B3, and Bn is independently a natural, a modified, or an unnatural nucleobase;
- each Z1 and Z2 is independently hydrogen, fluorine, —OH, —SH, —CH3, —CH2CH3, —OCH3, —OCH2CH3, —SCH3, —NH2, NHCH3, or NHC(═O)CH3;
- Z3 is —OCH3;
- each Z4, and Zn is independently hydrogen, fluorine, —OH, —SH, —CH3, —CH2CH3, —OCH3, —NH2, —NHCH3, —NH(C(═O)CH3), —OCH2CH3, —OCH2OCH3, —OCH2CH2CH3, —OCH(CH3)2, —SCH3, or —OCH2CH2OCH3;
- each Q1 and Q4 is independently —CH2—, —CH═CH—, —CH2O—, —CH2S—, —CH2CH2—, —CH2CF2—, —CH2NH2—, —CH2NH(CH3)—, or —CH2N(C(═O)CH3)—;
- each Q2 and Q3 is independently —O—, —S—, —CH2—, —CF2—, —NH—, —N(CH3)—, or —N(C(═O)CH3)—;
- X4 is —OH or —O−;
- each X1, X2, X3, and Xn is independently —OH, —SH, —O−, —S−, —NH2, —NHCH3, —NH(C(═O)CH3), —CH3, —CH2CH3, —CH2CH2CH3, —CH(CH3)2, —OCH3, or —OCH2CH3;
- Y4 is ═S;
- each Y1, Y2, Y3 and Yn is independently ═O, ═S, ═NH, or ═NCH3;
- each A, A1, and A2 is independently —O—, —S—, —CH2—, —NH—, —N(CH3)— or —N(C(═O)CH3)—;
- and
- p=0, 1, 2, 3, 4, 5 or 6,
- wherein the compound comprises a phosphorothioate, and where the phosphorothioate comprises a chiral phosphorous center.
-4. (canceled)
An in vitro-transcribed (IVT) mRNA sequence initiator comprising a compound of Formula (II) or a salt or solvate thereof:
- wherein
- B1 is
- each B2, B3, and Bn is independently a natural, a modified, or an unnatural nucleobase;
- each Z′ and Z″ is independently is hydrogen, fluorine, —OH, —SH, —CH3, —CH2CH3, —OCH3, —NH(CH3), —NH2, —NH(C(═O)CH3), or —SCH3;
- Z′″ is hydrogen, fluorine, —CH3, —CH2CH3, —OCH3, or —OCH2CH3;
- each Z1 and Z2 is independently hydrogen, fluorine, —OH, —SH, —CH3, —CH2CH3, —OCH3, —SCH3, —OCH2CH3, —NH2, NHCH3, or NHC(═O)CH3;
- each Z3, Z4, and Zn is independently hydrogen, fluorine, —OH, —CH3, —CH2CH3, —OCH3, —NH2, —NHCH3, —NH(C(═O)CH3), —OCH2CH3, —OCH2OCH3, —OCH2CH2CH3, —OCH(CH3)2, —SCH3, or —OCH2CH2OCH3;
- each Q1 and Q4 is independently —CH═CH—, —CH2—, —CH2O—, —CH2S—, —CH2CH2—, —CH2CF2—, —CH2NH2—, —CH2NH(CH3)—, or —CH2N(C(═O)CH3)—;
- each Q2 and Q3 is independently —O—, —S—, —CH2—, —CF2—, —NH—, —N(CH3)—, or —N(C(═O)CH3)—;
- each X1, X2, X3, X4, and Xn is independently —OH, —SH, —O−, —S−, —NH2, —NHCH3, —NH(C(═O)CH3), —CH3, —CH2CH3, —CH2CH2CH3, —CH(CH3)2, —OCH3 or —OCH2CH3;
- each Y1, Y2, Y3, Y4, and Yn is independently ═O, ═S, ═NH, or ═NCH3;
- each A, A1, and A2 is independently —O—, —S—, —CH2—, —NH—, —N(CH3)— or —N(C(═O)CH3)—;
- and
- p=0, 1, 2, 3, 4, 5 or 6.
An in vitro-transcribed (IVT) mRNA sequence initiator comprising a compound of Formula (III) or a salt or solvate thereof:
- wherein
- B1 is
- B2 is a modified or unnatural nucleobase;
- each B3, and Bn is independently a natural, a modified, or an unnatural nucleobase;
- each Z1 and Z2 is independently hydrogen, fluorine, —OH, —SH, —CH3, —CH2CH3, —OCH3, —OCH2CH3, —SCH3, —NH2, NHCH3, or NHC(═O)CH3;
- each Z3, Z4, and Zn is independently hydrogen, fluorine, —OH, —SH, —CH3, —CH2CH3, —OCH3, —NH2, —NHCH3, —NH(C(═O)CH3), —OCH2CH3, —OCH2OCH3, —OCH2CH2CH3, —OCH(CH3)2, —SCH3, or —OCH2CH2OCH3;
- each Q1 and Q4 is independently —CH2—, —CH═CH—, —CH2O—, —CH2S—, —CH2CH2—, —CH2CF2—, —CH2NH2—, —CH2NH(CH3)—, or —CH2N(C(═O)CH3)—;
- each Q2 and Q3 is independently —O—, —S—, —CH2—, —CF2—, —NH—, —N(CH3)—, or —N(C(═O)CH3)—;
- each X1, X2, X3, X4, and Xn is independently —OH, —SH, —O−, —S−, —NH2, —NHCH3, —NH(C(═O)CH3), —CH3, —CH2CH3, —CH2CH2CH3, —CH(CH3)2, —OCH3, or —OCH2CH3;
- each Y1, Y2, Y3, Y4, and Yn is independently ═O, ═S, ═NH, or ═NCH3;
- each A, A1, and A2 is independently —O—, —S—, —CH2—, —NH—, —N(CH3)— or —N(C(═O)CH3)—;
- and
- p=0, 1, 2, 3, 4, 5 or 6.
-8. (canceled)
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-13. (canceled)
-17. (canceled)
-23. (canceled)
-31. (canceled)
-35. (canceled)
-162. (canceled)
-169. (canceled)
Dependencies are inferred from the claim text.