Mesoporous silica-coated upconversion nanocrystals for near infrared light-triggered control of gene expression in zebrafish.

Aim: To develop a platform technology for photoactivation of gene expression in deep tissues.

Materials & Methods: Upconversion nanoparticles (UCNs) were synthesized from rare earth elements like Ytterbium, Yttrium and Thulium. The nanoparticles were then further coated with a layer of mesoporous silica and loaded with photomorpholinos or photocaged plasmids and tested in zebrafish. The UCNs were activated using safe near-infrared (NIR) light which in turn produced UV light locally to enable photoactivation in deep tissues.

Results: Light-controlled gene knockdown was demonstrated in an in vivo model, namely zebrafish. UCNs loaded with photomorpholinos were used to knockdown a gene - ntl, which is essential for notochord formation and mesoderm patterning in zebrafish using NIR light. UCN-mediated light-controlled gene expression was also achieved by expressing GFP in tumor cells transplanted into adult zebrafish by irradiating the fish with NIR light. Apart from the delivery and control of genes, the UCNs were also used as imaging agents to image both zebrafish embryos and adult zebrafish. enabled excellent background-free, fluorescent imaging of both embryos and adult zebrafish.

Conclusion: This technique of controlling gene expression/knockdown through NIR using UCNs is a game changer in the field of genetic manipulation and has the potential of being an excellent, safe and easy to implement tool for developmental biologists to investigate the role of specific genes in development. However, this technique is not restricted to be used only in zebrafish and can be extended for use in other animal models and even for clinical use, in various gene therapy applications.