Traceable Nano‐Biohybrid Complexes by One‐Step Synthesis as CRISPR‐Chem Vectors for Neurodegenerative Diseases Synergistic Treatment

Abstract

Abnormal protein aggregations are essential pathological features of neurodegenerative diseases. Eliminating while inhibiting the regeneration of these protein aggregates is considered an effective treatment strategy. Herein, the CRISPR/Cas9 gene‐editing tool is employed to inhibit the regeneration of disease‐related proteins, while chemical drugs are applied to eliminate the proteins that are produced. To efficiently deliver CRISPR‐chem drugs into brain lesions, traceable nano‐biohybrid complexes (F‐TBIO) are constructed by one‐step synthesis and CRISPR/Cas9 plasmids (CF‐TBIO) are loaded in a controllable manner. CF‐TBIO can knock out the BACE1 gene and reduce the burden of amyloid‐β, and thereby significantly improve the cognitive abilities of 2xTg‐AD mice. In particular, by prolonging the dosing interval, the pathological damage and behavioral abilities of 2xTg‐AD mice are still significantly improved. During the therapeutic process, CF‐TBIO with a high relaxation rate provides accurate imaging signals in the complex brain physiological environment. The finding shows that CF‐TBIO has great potential to serve as a CRISPR‐chem drug‐delivery platform for neurodegenerative diseases therapy.

A hypoxia-dissociable siRNA nanoplatform for synergistically enhanced chemo-radiotherapy of glioblastoma

“…When the BBB model was established, free FAM siRNA or RDPP(Met)/FAM-siRNA was added and observed at different time points. 32 Compared with free FAM siRNA, the cumulative transport ratio of RDPP(Met)/FAM-siRNA was significantly higher (Fig. 2B), showing effective BBB penetration.…”

Nucleic acid drug vectors for diagnosis and treatment of brain diseases

“…The protease reduced the positive surface charges on the hybrid complexes by catalyzing the hydrolysis of the polylysine, which released the CRISPR plasmids. 192 …”

CRISPR/Cas9 Delivery System Engineering for Genome Editing in Therapeutic Applications

“…The programmed delivery and targeting pathway could effectively reduce the off-target toxicity in normal cells. Recently, Shen et al [ 44 ] designed a multi-functional nanovector for the co-delivery of CRISPR/Cas9 plasmids and Fluvastatin into brain lesions. As illustrated in Figure 6 A, synthetic DOPA-Polylysine were coupled with Fluvastatin or rabies virus glycoproteins (RVG) through PEG, generating the long-chain bio-polycations (DOPA-PLys-PEG-Flu/RVG).…”

“…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.…”