Aptamers as Therapy for congenital Neutropenia Diseases

Dyskeratosis congenita (DC) is a rare disease caused by mutations in telomerase complex or telomeric proteins. Mutations in telomerase are part of
the genes panel that cause bone marrow disorders. This enzyme consists mainly of a protein component (TERT) and an RNA component (TERC).
The mutation of Telomerase RNA component, TERC, causes myelodysplastic syndrome and even acute myeloid leukemias. Recently and thanks to
the use of the zebrafish model, we have shown that TERC has a fundamental role in the formation of the myeloid lineage and this new function is
exerted independently of that performed at the telomeres. We now know that TERC regulates the expression of the major genes controlling
myelopoiesis by binding to regulatory regions and recruiting the transcription machinery to their promoters. In-depth knowledge of TERC’s mechanism
of action has allowed us to design aptamers (small oligonucleotides) that mimic the behavior of the entire Telomerase RNA (TERC) molecule,
providing an alternative to other current drugs for neutropenias and Myelodysplastic Syndrome (MDS).