Facebook PixelGene therapy to restore color vision in adults may be more effective if Oct4, Sox2, and Klf4 genes are expressed
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Gene therapy to restore color vision in adults may be more effective if Oct4, Sox2, and Klf4 genes are expressed

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Darko Savic
Darko Savic May 08, 2022
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To make color vision restoration gene therapy work in adults who have lost neuroplasticity, include the expression of Oct4, Sox2, and Klf4 genes in the polycistron.
  • Restoring color vision with gene therapies seems to be doable in children, but it gets more difficult in adults because they've lost the necessary neuronal plasticity. Including the expression of OSK could fix this.
  • Color vision restoration gene therapy is possible but not yet safe. By the time it becomes safe it could be too late for adults (who are still children today). Today it's possible but not safe, in the near future it will be safe but not possible (in adults). This idea might solve the paradox.
How it works
Gene therapy A: Color vision restoration
Gene therapies that restore color vision in colorblind people are underway and appear to be safe.
The parts of the brain that process vision increasingly lose plasticity in adulthood. Since the brains of people with color blindness have never learned to process color information, they need at least some plasticity to process the retina’s newly acquired (post gene therapy) ability to translate colors into visual impressions.
Gene therapy B: Partial cellular reprogramming to recover youthful epigenetic information
Ectopic expression of Oct4, Sox2 and Klf4 genes (OSK) in mouse retinal ganglion cells restores youthful DNA methylation patterns and transcriptomes, promotes axon regeneration after injury, and reverses vision loss in a mouse model of glaucoma and in aged mice. The beneficial effects of OSK-induced reprogramming in axon regeneration and vision require the DNA demethylases TET1 and TET2.
Combining the the above 2 gene therapies should make color vision restoration possible in adults. Therapy A fixes the color vision problem, therapy A makes the neurons/nerves plastic and able to learn new tricks again.
Semax could also play a role in the therapy. It's a synthetic analog of adrenocorticotropic hormone 4-10 that is known for both neuroprotective and neurotrophic effects.

[1]Fischer MD, Michalakis S, Wilhelm B, et al. Safety and Vision Outcomes of Subretinal Gene Therapy Targeting Cone Photoreceptors in Achromatopsia: A Nonrandomized Controlled Trial. JAMA Ophthalmol. 2020;138(6):643–651. doi:10.1001/jamaophthalmol.2020.1032

[2]Lu, Y., Brommer, B., Tian, X. et al. Reprogramming to recover youthful epigenetic information and restore vision. Nature 588, 124–129 (2020). https://doi.org/10.1038/s41586-020-2975-4

[3]Polunin GS, Nurieva SM, Baiandin DL, Sheremet NL, Andreeva LA. Opredelenie terapevticheskoĭ éffektivnosti novogo otechestvennogo preparata "Semaks" pri zabolevaniiakh zritel'nogo nerva [Evaluation of therapeutic effect of new Russian drug semax in optic nerve disease]. Vestn Oftalmol. 2000 Jan-Feb;116(1):15-8. Russian. PMID: 10741256.

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