The disclosure provides cyclic dinucleotides that are useful as STING agonists, pharmaceutical compositions and vaccines comprising the cyclic dinucleotides, and methods of treating diseases and disorders using the cyclic dinucleotides, pharmaceutical compositions, and vaccines.

The disclosure provides cyclic dinucleotides that are useful as STING agonists, pharmaceutical compositions and vaccines comprising the cyclic dinucleotides, and methods of treating diseases and disorders using the cyclic dinucleotides, pharmaceutical compositions, and vaccines.

The present invention relates to a method for producing a compound represented by general formula [C-1-1], which comprises: a step for reacting a compound represented by general formula [B-1-1] with a compound represented by general formula [P] to form a compound represented by general formula [B-1-2]; and a step for reacting the compound represented by general formula [B-1-2] with a compound represented by general formula [A-1] to form the compound represented by general formula [C-1-1].

The present invention relates to a method for producing a compound represented by general formula [C-1-1], which comprises: a step for reacting a compound represented by general formula [B-1-1] with a compound represented by general formula [P] to form a compound represented by general formula [B-1-2]; and a step for reacting the compound represented by general formula [B-1-2] with a compound represented by general formula [A-1] to form the compound represented by general formula [C-1-1].

Compositions and methods for modulating expression of target nucleic acids using a single strand oligoribonucleotide ss-siRNA compound are disclosed.

Compositions and methods for modulating expression of target nucleic acids using a single strand oligoribonucleotide ss-siRNA compound are disclosed.

This specification discloses a novel methodology for labelling RNA via enzymatic incorporation of a minimally perturbing fluorescent tricyclic cytosine analogue. This analogue is shown to be 100% incorporated in example transcripts and is fully compatible with both in vitro and in cell transcription. Spectroscopic characterization shows that the incorporation rate of the cytosine analogue is on par with its natural counterpart. Using live cell imaging and flow cytometry, labelled mRNAs are efficiently and correctly translated upon transfection into living cells and cell-free systems. The spectral properties of the modified transcripts and their correct translation product allow for their straightforward and simultaneous visualization. This technology therefore offers a general route to understanding the biological behaviour of RNA of interest, including RNA based drugs. The fluorescent tricyclic cytosine analogue has formula (I):

##STR00001##

This specification discloses a novel methodology for labelling RNA via enzymatic incorporation of a minimally perturbing fluorescent tricyclic cytosine analogue. This analogue is shown to be 100% incorporated in example transcripts and is fully compatible with both in vitro and in cell transcription. Spectroscopic characterization shows that the incorporation rate of the cytosine analogue is on par with its natural counterpart. Using live cell imaging and flow cytometry, labelled mRNAs are efficiently and correctly translated upon transfection into living cells and cell-free systems. The spectral properties of the modified transcripts and their correct translation product allow for their straightforward and simultaneous visualization. This technology therefore offers a general route to understanding the biological behaviour of RNA of interest, including RNA based drugs. The fluorescent tricyclic cytosine analogue has formula (I):

##STR00001##

A modified cytidine compound, that is, an aminooxy group is modified at the 4-position of a cytidine pyrimidine ring to produce derivative cytidine and nucleic acid containing the derivative cytidine, such as RNA. The expression level of the nucleic acid containing the modified cytidine, in particular mRNA, in the body is significantly improved.

A modified cytidine compound, that is, an aminooxy group is modified at the 4-position of a cytidine pyrimidine ring to produce derivative cytidine and nucleic acid containing the derivative cytidine, such as RNA. The expression level of the nucleic acid containing the modified cytidine, in particular mRNA, in the body is significantly improved.