Oct4-Sox2-Klf4 transcription factor complex (OSK)

The Oct4-Sox2-Klf4 (OSK) transcription factor complex is a subset of the Yamanaka factors used to induce partial cellular reprogramming in specialized tissues like the retina (Takahashi & Yamanaka, 2006, Cell). In retinal ganglion cells (RGCs), the expression of OSK is targeted to reverse the epigenetic clock and restore youthful physiological functions, such as the ability to regenerate axons after injury (Lu et al., 2020, Nature). This therapeutic approach relies on the interaction between OSK and the cell's epigenetic machinery, specifically the recruitment of Ten-eleven translocation (TET) enzymes that catalyze DNA demethylation at age-associated loci (Wu et al., 2020, Nature). By resetting the DNA methylation landscape, OSK restores a youthful transcriptional program that promotes survival and functional recovery in models of glaucoma and age-related vision loss. Current drug development, such as that by Life Biosciences, utilizes adeno-associated virus (AAV) vectors to deliver OSK genes to the eye, aiming to treat optic neuropathies without inducing pluripotency or tumorigenesis (Life Biosciences, 2024). This strategy represents a shift from traditional neuroprotection toward active epigenetic rejuvenation of damaged neurons.

Other names

OSK factorsPartial reprogramming factorsYamanaka factors (excluding c-Myc)Epigenetic rejuvenation complexPOU5F1-SOX2-KLF4 complex

Induction of partial cellular reprogramming through the recruitment of Ten-eleven translocation (TET) DNA demethylases to restore youthful DNA methylation patterns and gene expression profiles (Lu et al., 2020, Nature).