Zinc finger and SCAN domain containing 4 (ZSCAN4)

Zinc finger and SCAN domain containing 4 (ZSCAN4) is a transcription factor that plays a pivotal role in maintaining telomere length and genomic stability during early embryonic development and in pluripotent stem cells (Zalzman et al., 2010, Nature). Unlike the telomerase-dependent pathway, ZSCAN4 facilitates telomere elongation through a recombination-mediated mechanism, which is essential for the long-term survival and karyotype stability of embryonic stem cells (Amano et al., 2013, Nature Communications). In the context of regenerative medicine, ZSCAN4 is being utilized as a therapeutic agent to rejuvenate hematopoietic stem cells (HSCs) in patients with telomere biology disorders such as Dyskeratosis congenita and aplastic anemia (Ko et al., 2016, Stem Cells). By employing a temperature-sensitive Sendai virus (SeV) vector for ex vivo transduction, ZSCAN4 can be transiently expressed in CD34+ cells without the risk of permanent genomic integration, as SeV replicates exclusively in the cytoplasm (Nakanishi & Iida, 2012, Journal of Controlled Release). This transient pulse of ZSCAN4 expression leads to rapid telomere extension and enhances the functional fitness of the stem cell pool (Nishinosono et al., 2019, Scientific Reports). This approach represents a novel gene therapy strategy aimed at restoring hematopoiesis by addressing the underlying molecular defect of stem cell exhaustion.

Other names

ZSCAN4Zinc finger and SCAN domain-containing protein 4ZNF494ZSCAN4W

Transient expression of the ZSCAN4 protein to induce rapid telomere elongation through a recombination-based mechanism (ALT-like), thereby restoring the proliferative capacity and genomic integrity of hematopoietic stem cells.