Ribonucleotide reductase regulatory subunit M2 (RRM2) mRNA (RRM2 mRNA)

Ribonucleotide reductase regulatory subunit M2 (RRM2) mRNA is the messenger RNA transcript encoding the small subunit of the ribonucleotide reductase (RR) enzyme, which catalyzes the conversion of ribonucleoside diphosphates to deoxyribonucleoside diphosphates (dNTPs) (UniProt P31350). This process is the rate-limiting step for de novo DNA synthesis and is essential for DNA replication and repair (PubMed PMID: 15150587). RRM2 is frequently overexpressed in various malignancies, including solid tumors and hematological cancers, where it correlates with increased tumor aggressiveness and resistance to chemotherapy (PubMed PMID: 17404095). GTI-2040 (also known as LOR-2040) is a 20-base phosphorothioate antisense oligonucleotide designed to specifically target and hybridize with the RRM2 mRNA (PubMed PMID: 16432188). This binding triggers RNase H-mediated degradation of the mRNA, leading to a reduction in RRM2 protein levels and subsequent depletion of intracellular dNTP pools, which inhibits tumor cell proliferation and induces apoptosis (PubMed PMID: 12124345). Clinical trials have investigated GTI-2040 as both a single agent and in combination with cytotoxic drugs like gemcitabine or cytarabine to enhance therapeutic outcomes in patients with advanced cancers (ClinicalTrials.gov).

Other names

R2 mRNARR2 mRNARibonucleoside-diphosphate reductase subunit M2 mRNA

Antisense oligonucleotide-mediated mRNA degradation via RNase H recruitment