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

Programmed cell death 1 (PD-1) pre-messenger RNA is the primary transcript of the PDCD1 gene, serving as the precursor to the mature mRNA that encodes the PD-1 immune checkpoint receptor [2, 3]. PD-1 is a critical regulator of T-cell activity, typically acting as a "brake" on the immune system to prevent autoimmunity; however, tumors often exploit this pathway to evade immune detection [10, 11]. Targeting the pre-mRNA stage offers a unique therapeutic strategy by modulating alternative splicing or inducing RNA degradation before the functional protein is even produced [4, 8]. For example, therapeutic interventions such as antisense oligonucleotides (ASOs) can induce exon skipping to generate soluble PD-1 isoforms (sPD-1) that act as natural decoys, or they can reduce the overall expression of the membrane-bound receptor [5, 6]. This RNA-level modulation aims to restore anti-tumor immunity and may offer advantages over traditional monoclonal antibodies, such as different pharmacokinetic profiles or the ability to target specific cell populations [4, 8]. Research into PD-1 pre-mRNA targeting is currently focused on overcoming T-cell exhaustion in various cancers and chronic infections [14, 21].

Other names

PDCD1 pre-mRNACD279 pre-mRNAProgrammed cell death protein 1 precursor mRNAPD-1 precursor mRNA

Splicing modulation through exon skipping (e.g., Exon 2 or 3) or blocking of exonic splicing enhancers (ESEs) to reduce membrane-bound PD-1 expression and/or increase the production of soluble PD-1 (sPD-1) isoforms [3, 4, 8].