Phosphate replacement mRNA cap analogs
The present disclosure relates to cap analogs, which can result in high levels of capping efficiency and transcription and improved translation efficiencies. The present disclosure also relates to methods useful for preparing cap analogs and using mRNA species containing such analogs, as well as kits containing the novel cap analogs.
1. An RNA molecule having a 5′ end comprising a compound of formula (III):
wherein
indicates the attachment point of the 5′ end to the RNA molecule;
B 1 is
wherein
indicates the attachment point of B 1 to the compound;
R a , R b , and R c are H;
R 1 is CH 3 ;
B 2 is
wherein
indicates the attachment point of B 2 to the compound;
R d , R e , and R f are H;
X 1 is N or N + (CH 3 );
X 2 is O;
R 20 , R 21 , R 22 , and R 23 are H;
R 27 and R 28 are OH;
R 2 is OR 3 ;
R 3 is H or CH 3 ; and
Y 2 is
wherein
indicates the attachment points of Y 2 to the compound.
2. The RNA molecule of claim 1 , wherein X 1 is N.
3. The RNA molecule of claim 1 , wherein R 3 is CH 3 .
4. The RNA molecule of claim 1 , wherein X 1 is N + (CH 3 ).
5. The RNA molecule of claim 1 , wherein R 3 is H.
6. The RNA molecule of claim 1 , wherein R 3 is H and X 1 is N.
7. The RNA molecule of claim 1 , wherein R 3 is H and X 1 is N + (CH 3 ).
8. The RNA molecule of claim 1 , wherein R 3 is CH 3 and X 1 is N + (CH 3 ).
9. The RNA molecule of claim 1 , having a 5′ end comprising
wherein
indicates the attachment point of the 5′ end to the RNA molecule.
10. The RNA molecule of claim 9 , wherein X 1 is N.
11. The RNA molecule of claim 9 , wherein R 3 is CH 3 .
12. The RNA molecule of claim 9 , wherein X 1 is N + (CH 3 ).
13. The RNA molecule of claim 9 , wherein R 3 is H.
14. The RNA molecule of claim 9 , wherein R 3 is H and X 1 is N.
15. The RNA molecule of claim 9 , wherein R 3 is H and X 1 is N + (CH 3 ).
16. The RNA molecule of claim 9 , wherein R 3 is CH 3 and X 1 is N + (CH 3 ).
17. The RNA molecule of claim 9 , wherein the RNA molecule has a half-life that is at least 1.2 times of that of an RNA molecule of the same polynucleotide sequence having a 5′ end comprising a natural triphosphate terminal RNA cap in a cellular environment.
18. The RNA molecule of claim 1 , having a 5′ end comprising
wherein
indicates the attachment point of the 5′ end to the RNA molecule.
19. The RNA molecule of claim 18 , wherein the RNA molecule has a half-life that is at least 1.2 times of that of an RNA molecule of the same polynucleotide sequence having a 5′ end comprising a natural triphosphate terminal RNA cap in a cellular environment.
20. The RNA molecule of claim 1 , wherein the RNA molecule has a half-life that is at least 1.2 times of that of an RNA molecule of the same polynucleotide sequence having a 5′ end comprising a natural triphosphate terminal RNA cap in a cellular environment.