Clusterin mRNA (CLU mRNA) (CLU mRNA)

Clusterin mRNA is the transcript of the CLU gene, which encodes a highly conserved, multifunctional glycoprotein that exists in several isoforms, most notably the secretory form (sCLU) and the nuclear form (nCLU) (UniProt P10909). The secretory isoform acts as an extracellular chaperone, preventing the aggregation of misfolded proteins and inhibiting apoptosis by interacting with Bax and Ku70, which promotes cell survival under stress conditions such as chemotherapy or radiation (PubMed: 21358605). In many cancers, including prostate and lung cancer, clusterin is significantly upregulated as a survival mechanism, contributing to treatment resistance and disease progression (PubMed: 28103458). Therapeutic targeting of clusterin mRNA has primarily utilized antisense oligonucleotides (ASOs) like custirsen (OGX-011), which bind to the mRNA sequence to trigger RNase H-mediated degradation, thereby reducing protein levels and sensitizing tumors to standard therapies (PubMed: 19841325). Beyond oncology, clusterin is the third most prominent genetic risk factor for late-onset Alzheimer's disease, where it is involved in amyloid-beta clearance and neuroinflammation (PubMed: 24507018). Despite its strong biological rationale, clinical development of clusterin mRNA inhibitors has been hindered by the failure of late-stage trials to demonstrate a significant overall survival benefit in unselected patient populations.

Other names

Apolipoprotein J mRNAComplement lysis inhibitor mRNATRPM-2 mRNASGP-2 mRNACLU

Antisense oligonucleotide-mediated degradation of mRNA via RNase H, leading to inhibition of protein translation (PubMed: 19841325).