Myeloid cell surface antigen CD33 (CD33) mRNA (CD33 mRNA)

Myeloid cell surface antigen CD33 (CD33) mRNA is the transcript of the CD33 gene, which encodes a transmembrane receptor belonging to the sialic acid-binding immunoglobulin-like lectin (Siglec) family (UniProt: P20248). It is primarily expressed on the surface of myeloid lineage cells, including monocytes, macrophages, and microglia, where it typically functions as an inhibitory receptor to maintain immune homeostasis (PubMed: 23644458). In oncology, CD33 is a prominent target for Acute Myeloid Leukemia (AML), with its mRNA serving as the template for the protein targeted by antibody-drug conjugates like Gemtuzumab ozogamicin (FDA: Mylotarg Label). In neurology, CD33 mRNA has gained significant attention as a target for Alzheimer's disease; genetic studies have identified that the rs3865444 SNP modulates the splicing of CD33 mRNA (PubMed: 23644456). Therapeutic strategies using antisense oligonucleotides (ASOs) aim to target the mRNA to induce exon 2 skipping, producing a shorter isoform (CD33m) that lacks the ligand-binding domain and enhances the ability of microglia to clear amyloid-beta plaques (PubMed: 30250114). This mRNA-level modulation offers a precise mechanism to alter protein function and disease progression in neurodegenerative contexts. Additionally, RNA interference (RNAi) technologies can be used to silence CD33 mRNA expression in conditions where protein overexpression contributes to pathology (PubMed: 24613133). Overall, CD33 mRNA represents a versatile therapeutic node for both protein-depletion strategies in cancer and splicing-modulation strategies in neurodegeneration.

Other names

SIGLEC3 mRNASialic acid-binding Ig-like lectin 3 mRNAp67 mRNAgp67 mRNA

Antisense oligonucleotides (ASOs) target CD33 mRNA to modulate alternative splicing, specifically inducing the skipping of exon 2 to favor the protective CD33m isoform (PubMed: 30250114). Other RNA-targeted approaches may use siRNA or ASOs to trigger RNase H-mediated degradation of the transcript to reduce overall CD33 protein expression (PubMed: 24613133).