“…Alternative applications within the scope of gene therapy exploiting constitutive activation of TERT in cancer utilize silencing or inhibition of TERT or TERC activity [76,77,78]. For example, siRNA or antisense RNA targeting TERT has been an actively investigated gene therapeutic of choice [79,80,81,82,83,84], with a small number of reports exploring different strategies (such as expression of c-terminal TERT polypeptide (hTERTC27) [85,86,87], CRISPR/Cas9 targeting an oncogenic TERT promoter mutant allele that enables constitutive activation in cancer [88], or microRNA-mediated downregulation of TERT by targeting of the 3′-UTR region [89]). In general, these approaches promote cellular senescence, induce apoptotic tumor cell death, and attenuate the rate of proliferation.…”