Programmed cell death 1 pre-messenger RNA (PDCD1 pre-mRNA)

PDCD1 pre-mRNA is the primary transcript of the Programmed Cell Death 1 (PDCD1) gene, which encodes the PD-1 protein, a critical inhibitory receptor and immune checkpoint (NCBI Gene ID: 5133). PD-1 is primarily expressed on activated T cells and plays a vital role in maintaining peripheral tolerance and preventing autoimmunity by binding to its ligands, PD-L1 and PD-L2 (UniProt: Q15116). In many cancers, the PD-1 pathway is hijacked to suppress the anti-tumor immune response, leading to T-cell exhaustion and tumor progression. While monoclonal antibodies targeting the PD-1 protein are standard of care, targeting the PDCD1 pre-mRNA offers a novel therapeutic avenue to modulate PD-1 expression at the genetic level (PubMed: 33458156). Strategies such as antisense oligonucleotides (ASOs) can be designed to induce exon skipping, which results in the production of non-functional or soluble PD-1 isoforms, or to promote the degradation of the transcript (PubMed: 31235878). This approach potentially allows for more precise control over PD-1 signaling and may provide therapeutic benefits in patients who are refractory to traditional protein-targeting biologics.

Other names

PD-1 pre-mRNACD279 pre-mRNAProgrammed cell death 1 precursor RNAPDCD1 transcript

Modulation of pre-mRNA splicing (e.g., exon skipping) or RNase H-mediated degradation to reduce functional PD-1 protein expression.