Figure 6.

Illustration of CRISPR/Cas9 nano-biohybrid complexes for neurodegenerative diseases treatment. (A) Preparation of CF-TBIO and illustration of the therapeutic mechanism. CF-TBIO were injected through the tail vein. CF-TBIO nanoparticle crossed the BBB and targeted neurons with the guidance of RVG. The ester bonds were hydrolyzed by intracellular esterase and release Fluvastatin to clear Aβ. CRISPR/Cas9 plasmids then entered the nuclei and knocked out the BACE1 gene. (B) Diagram of CRISPR/Cas9 plasmids and Fluvastatin for AD treatment. (C) T7E1 assay for BACE1 indels frequency analysis in brains of double transgenic (2×Tg-AD) mice. (D) Quantification of WB analysis of Aβ expression. (i) Wild type mice without treatment, (ii) 2×Tg-AD mice without treatment, (iii) 2×Tg-AD mice treated with CNSF-TBIO, (iv) CF/TEIO, (v) CF-TBIO, (vi) the mice were administrated via the tail vein every 10 days, while the other groups were every 3 days. Significant differences between groups were indicated as * p < 0.05, and ** p < 0.01. Reproduced with permission from [44]. Copyright Joh Wiley and Sons, 2021.