MicroRNAs
The Nobel Assembly at the Karolinska Institutet has decided to award the 2024 Nobel Prize in Physiology or Medicine jointly to Victor Ambros and Gary Ruvkun “for the discovery of microRNA and its role in post-transcriptional gene regulation.” The first miRNA was discovered from Caenorhabditis elegans in 1993. Victor Ambros and Gary Ruvkun confirmed that lin-4 RNAs could regulate translation of the gene Lin-14 through an antisense mechanism. Since then, thousands of miRNAs have been gradually discovered in almost all groups of animals and plants, including humans, mice, rats, zebrafish, fruit flies, rice, arabidopsis, etc.
MicroRNAs (miRNAs ) are a class of endogenous non-coding RNAs (21-23 nt) that bind to target genes and regulate their expression. MiRNAs form RNA induced silencing complex (RISC) with various protein components that trigger endogenous RNA interference by regulating the stability or inducing mRNA degradation. MiRNAs are frequently altered in disease owing to genomic events, such as mutations, deletion amplification or transcriptional changes, or to biogenesis defects due to mutations or the downregulation of enzymes that regulate miRNA biogenesis.
Advances in the development of oligonucleotide chemistry have allowed for development of engineered oligonucleotides directed against specific miRNAs. MiRNA-based therapeutics can be divided into miRNA mimics and inhibitors of miRNAs (also known as antimiRs). MiRNA mimics are synthetic double-stranded small RNA molecules that match the corresponding miRNA sequence and therefore functionally aim to replenish the lost miRNA expression in diseases. By contrast, antimiRs are single stranded and based on first-generation antisense oligonucleotides (ASOs), which had been designed to target mRNAs, or modified with locked nucleic acids (LNAs). AntimiRs with a 2ʹ-O-methoxyethyl modification are also called antagomiRs. These synthetic small RNA molecules have a complementary sequence to the miRNA to be inhibited and block the function of the corresponding miRNA by binding to it strongly.
PE6g mRNA (N1-methyl-pseudouridine) is an enzyme encoding the optimized primer editor PE6g, improving editing efficiency, used for efficient and precise gene editing.
tdTomato mRNA (N1-methyl-pseudouridine) is a bright red fluorescent protein, tdTomato, used for fluorescent labeling, cell tracking, and expression detection. Its excitation and emission peaks are at 554 nm and 581 nm, respectively.
MAD7 mRNA (N1-methyl-pseudouridine) encodes the nuclease MAD7. MAD7 requires only crRNA to achieve gene editing and can specifically target AT-rich regions in the genome. Furthermore, MAD7 cuts DNA through mismatch cleavage.
F-Luc Self-Amplifying RNA (5-methylcytidine) is a self-amplifying RNA encoding the firefly luciferase F-Luc, used for in vivo bioluminescence imaging and quantitative gene expression detection. After efficiently entering cells or animals, F-Luc mRNA can be translated into F-Luc and emit bioluminescence in the presence of its substrate, luciferin.
eGFP Self-Amplifying RNA (5-methylcytidine) is a self-amplifying RNA encoding enhanced green fluorescent protein eGFP, which can be expressed for extended periods at low doses and is used as a reporter gene and transfection tracing gene. The expressed protein is excited at 488 nm and emitted at 507 nm.
hsa-let-7f-5p mimic is a synthetic double-stranded microRNA used to overexpress mature let-7f-5p in cells for mimicking its tumor-suppressive function. hsa-let-7f-5p mimic is predicted to inhibit the expression of SLC5A5 and INSR. hsa-let-7f-5p mimic can be applied to research related to thyroid cancer and pancreatic ductal adenocarcinoma.
hsa-miR-302b-3p agomir is a chemically synthesized miRNA mimic that mimics endogenous miRNAs, upregulates miRNA activity, and is used for gain-of-function studies.
hsa-miR-23b-3p inhibitors are chemically-modified oligonucleotides that hybridize with mature miRNAs. The miRNA inhibitors have full-length nucleotide 2'-methoxy modification. The miRNA inhibitors strongly compete with mature miRNAs to prevent the complementary pairing of miRNAs and their target genes, thereby inhibiting miRNAs from functioning.
mmu-miR-139-3p inhibitors are chemically-modified oligonucleotides that hybridize with mature miRNAs. The miRNA inhibitors have full-length nucleotide 2'-methoxy modification. The miRNA inhibitors strongly compete with mature miRNAs to prevent the complementary pairing of miRNAs and their target genes, thereby inhibiting miRNAs from functioning.
mmu-miR-139-3p antagomirs are chemically-modified oligonucleotides that hybridize with mature miRNAs. The miRNA antagomirs have 2 phosphorothioates at the 5' end, 4 phosphorothioates at the 3' end, 1 cholesterol group at the 3' end, and full-length nucleotide 2'-methoxy modification. The miRNA antagomirs strongly compete with mature miRNAs to prevent the complementary pairing of miRNAs and their target genes, thereby inhibiting miRNAs from functioning. Stability of miRNA antagomirs appears to be significantly higher than miRNA inhibitors, they exhibits enhanced cellular uptake, stability and regulatory activity in vivo.
mmu-miR-139-3p agomirs are chemically-modified double-strand miRNA mimics with modified mature miRNA strand: 2 phosphorothioates at the 5' end, 4 phosphorothioates at the 3' end, 3' end cholesterol group, and full-length nucleotide 2'-methoxy modification. They are designed to mimic endogenous miRNAs and recommended for miRNA functional studies. Compared with miRNA mimics, they exhibits enhanced cellular uptake, stability and regulatory activity in vivo.
mmu-miR-449a-5p antagomir antagomirs are chemically-modified oligonucleotides that hybridize with mature miRNAs. The miRNA antagomirs have 2 phosphorothioates at the 5' end, 4 phosphorothioates at the 3' end, 1 cholesterol group at the 3' end, and full-length nucleotide 2'-methoxy modification. The miRNA antagomirs strongly compete with mature miRNAs to prevent the complementary pairing of miRNAs and their target genes, thereby inhibiting miRNAs from functioning. Stability of miRNA antagomirs appears to be significantly higher than miRNA inhibitors, they exhibits enhanced cellular uptake, stability and regulatory activity in vivo.
mmu-miR-449a-5p agomirs are chemically-modified double-strand miRNA mimics with modified mature miRNA strand: 2 phosphorothioates at the 5' end, 4 phosphorothioates at the 3' end, 3' end cholesterol group, and full-length nucleotide 2'-methoxy modification. They are designed to mimic endogenous miRNAs and recommended for miRNA functional studies. Compared with miRNA mimics, they exhibits enhanced cellular uptake, stability and regulatory activity in vivo.
rno-miR-122-5p agomirs are chemically-modified double-strand miRNA mimics with modified mature miRNA strand: 2 phosphorothioates at the 5' end, 4 phosphorothioates at the 3' end, 3' end cholesterol group, and full-length nucleotide 2'-methoxy modification. They are designed to mimic endogenous miRNAs and recommended for miRNA functional studies. Compared with miRNA mimics, they exhibits enhanced cellular uptake, stability and regulatory activity in vivo.
mmu-miR-210-3p inhibitors are chemically-modified oligonucleotides that hybridize with mature miRNAs. The miRNA inhibitors have full-length nucleotide 2'-methoxy modification. The miRNA inhibitors strongly compete with mature miRNAs to prevent the complementary pairing of miRNAs and their target genes, thereby inhibiting miRNAs from functioning.
