Telomerase reverse transcriptase mRNA (TERT mRNA) (TERT mRNA)

Human TERT mRNA is the messenger RNA transcript that encodes the telomerase reverse transcriptase (TERT) protein, the catalytic subunit of the telomerase enzyme complex (UniProt, 2024). This mRNA is a critical regulator of cellular lifespan, as it enables the synthesis of telomeric DNA repeats to prevent chromosomal shortening during division (NIH, 2023). While TERT mRNA is typically repressed in adult somatic cells, its reactivation is a hallmark of approximately 90% of human malignancies, providing cancer cells with unlimited replicative potential (PubMed, 2021). Consequently, TERT mRNA is targeted in oncology through antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs) that inhibit its translation or induce its degradation, as well as through mRNA-based vaccines that prime the immune system to recognize TERT-expressing cells (Frontiers in Oncology, 2021). Conversely, the transient delivery of synthetic TERT mRNA is being investigated as a pro-longevity therapy to extend telomeres in stem cells and treat telomere-shortening diseases like dyskeratosis congenita (Stanford University, 2015). Clinical development of these therapies aims to exploit the differential expression of TERT between cancerous and healthy tissues to achieve selective anti-tumor activity while minimizing effects on telomerase-positive normal cells (Nature Reviews Cancer, 2022).

Other names

hTERT mRNATelomerase catalytic subunit mRNAHuman telomerase reverse transcriptase mRNATERT transcripthTERT transcript

Therapeutic agents targeting TERT mRNA operate through several distinct mechanisms: antisense oligonucleotides (ASOs) and siRNAs bind to the mRNA sequence via Watson-Crick base pairing to trigger RNase H-mediated cleavage or RISC-mediated degradation, thereby preventing the synthesis of the TERT protein. In immunotherapy, mRNA-based vaccines or DNA vaccines (which transcribe into TERT mRNA) deliver the genetic code for TERT to antigen-presenting cells, which then present TERT-derived peptides to T-cells to elicit a systemic anti-tumor immune response. Additionally, synthetic modified TERT mRNA can be delivered exogenously to transiently upregulate telomerase activity for regenerative purposes.