posted on 2021-02-15, 22:03authored byJiahua Li, Yafeng Hao, Huizhuo Pan, Yingying Zhang, Guohui Cheng, Baona Liu, Jin Chang, Hanjie Wang
Vascular
endothelial growth factor (VEGF) is the key regulator
in neovascular lesions. The anti-VEGF injection is a major way to
relieve retinal neovascularization and treat these diseases. However,
current anti-VEGF therapeutics show significant drawbacks. The reason
is the inability to effectively control its therapeutic effect. Therefore,
how to controllably inhibit the VEGF target is a key point for preventing
angiogenesis. Here, a CRISPR-dCas9 optogenetic nanosystem was designed
for the precise regulation of pathologic neovascularization. This
system is composed of a light-controlled regulatory component and
transcription inhibition component. They work together to controllably
and effectively inhibit the target gene’s VEGF. The opto-CRISPR
nanosystem achieved precise regulation according to individual differences,
whereby the expression and interaction of gene was activated by light.
The following representative model laser-induced choroid neovascularization
and oxygen-induced retinopathy were taken as examples to verify the
effect of this nanosystem. The results showed that the opto-CRISPR
nanosystem was more efficacious in the light control group (NV area
effectively reduced by 41.54%) than in the dark control group without
light treatment. This strategy for the CRISPR-optogenetic gene nanosystem
led to the development of approaches for treating severe eye diseases.
Besides, any target gene of interest can be designed by merely replacing
the guide RNA sequences in this system, which provided a method for
light-controlled gene transcriptional repression.