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.
- Molecular Weight: 13957.42
hsa-let-7d-3p mimics are small, chemically synthesized double-stranded RNAs that mimic endogenous miRNAs and enable miRNA functional analysis by up-regulation of miRNA activity.
- Molecular Weight: 13941.42
hsa-let-7b-3p mimics are small, chemically synthesized double-stranded RNAs that mimic endogenous miRNAs and enable miRNA functional analysis by up-regulation of miRNA activity.
- Molecular Weight: 13956.44
hsa-let-7a-2-3p mimics are small, chemically synthesized double-stranded RNAs that mimic endogenous miRNAs and enable miRNA functional analysis by up-regulation of miRNA activity.
- Formula: C₄₂₃H₅₂₉N₁₆₁O₃₀₅P₄₂
- Molecular Weight: 14049.50
Eldocasiran is a micro-ARN-193a-3p analogue, Eldocasiran has anticancer activity. Eldocasiran can be used for cancer research.
bta-miR-125a-5p 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.
LbCas12a mRNA V2 (N1-methyl-pseudouridine) encodes the genera *Cas12a* (LbCas12a, formerly Cpf1), possessing TTTN PAM and staggered cleavage characteristics, and is used for gene editing.
CD19 mRNA (N1-methyl-pseudouridine) encodes the B cell surface antigen CD19, used in CAR-T cell research and immunological studies. CD19 plays two main functions in human B cells: as an aptamer protein, recruiting cytoplasmic signaling proteins to the cell membrane; and within the CD19/CD21 complex, lowering the activation threshold of B cell receptor signaling pathways.
saCas9 mRNA (N1-methyl-pseudouridine) is an enzyme encoding Staphylococcus aureus Cas9 (saCas9), small in size and well-suited for AAV delivery. After efficiently entering cells or animals, saCas9 mRNA (N1-methyl-pseudouridine) can be translated into protein, thereby enabling gene editing functions within the cell.
mNeptune2.5 mRNA (N1-methyl-pseudouridine) is a far-red fluorescent protein, mNeptune2.5, with strong tissue penetration, used for deep in vivo fluorescence imaging and tracing. mNeptune2.5 protein can be excited in the visible light range at wavelengths greater than 600 nm.
Scarless CD19 CAR circular RNA (CVB3) is a circular RNA that uses CVB3 IRES to mediate scarless expression of the CD19 chimeric antigen receptor (CAR) for CAR-T cell research. This circular RNA features a scarless circularization design, eliminating the need for a linker or adapter sequence between the 5′ and 3′ ends, and achieving efficient circularization and expression without the need for optimized UTR elements.
