5-halouracil-modified microRNAs and their use in the treatment of cancer
The present disclosure provides nucleic acid compositions that incorporate one or more halouracil molecules. More specifically, the present disclosure reveals that the replacement of uracil nucleotides within a microRNA nucleotide sequence with a 5-halouracil increases the ability of the micro-RNA to inhibit cancer progression and tumorigenesis. As such, the present disclosure provides various nucleic acid (e.g., microRNA) compositions having 5-halouracil molecules incorporated in their nucleic acid sequences and methods for using the same. The present disclosure further provides pharmaceutical compositions comprising the modified nucleic acid compositions, and methods for treating cancers using the same.
1. A double-stranded nucleic acid comprising a modified microRNA nucleotide sequence that comprises uracil nucleic acids, wherein all the uracil nucleic acids including the seed region of the modified microRNA nucleotide sequence, which are complementary to a B-cell lymphoma 2 (BCL2) nucleotide sequence, are 5-fluorouracils, to combine the potency of microRNA nucleotide sequence and 5-fluorouracils, and wherein the modified microRNA nucleotide sequence binds to the B-cell lymphoma 2 (BCL2) nucleotide sequence that is complementary to the miR-129 microRNA nucleotide sequence set forth in SEQ ID NO: 1 or the miR-15a microRNA nucleotide sequence set forth in SEQ ID NO: 2.
2. A pharmaceutical composition comprising at least one double-stranded nucleic acid of claim 1 .
3. The pharmaceutical composition of claim 2 , wherein said modified microRNA nucleotide sequence comprises the miR-15a nucleotide sequence.
4. The pharmaceutical composition of claim 2 , wherein said modified microRNA nucleotide sequence comprises the miR-129 nucleotide sequence.
5. The double-stranded nucleic acid of claim 1 , wherein the modified microRNA nucleotide sequence comprises the miR-129 nucleotide sequence.
6. The double-stranded nucleic acid of claim 1 , wherein modified microRNA nucleotide sequence comprises the miR-15a nucleotide sequence.
7. The double-stranded nucleic acid of claim 6 , wherein the modified microRNA nucleotide sequence is UAGCAGCACAU F AAU F GGU F U F U F GU F G [SEQ ID NO. 7].