Abstract
The CRISPR-Cas13 system based on a bacterial enzyme has been explored as a powerful new method for RNA manipulation. Due to the high efficiency and specificity of RNA editing/interference achieved by this system, it is currently being developed as a new therapeutic tool for the treatment of neurological and other diseases. However, the safety of this new generation of RNA therapies is still unclear. In this study, we constructed a vector expressing CRISPR-Cas13 under a constitutive neuron-specific promoter. CRISPR-Cas13 from Leptotrichia wadei was expressed in primary cultures of mouse cortical neurons. We found that the presence of CRISPR-Cas13 impedes the development of cultured neurons. These results show a neurotoxic action of Cas13 and call for more studies to test for and possibly mitigate the toxic effects of Cas13 enzymes in order to improve CRISPR-Cas13-based tools for RNA targeting.
Highlights
The CRISPR-associated protein 13 (Cas13) was initially found in bacteria
Our results demonstrate that the Cas13 protein has a marked neurotoxic effect on the de-2 of 6 velopment and differentiation of cultured neurons
We demonstrate that expressing the CRISPR-Cas13 protein in mouse cerebral cortical results in that reduced neurite the growth and development, In this study,neurons we demonstrate expressing
Summary
The CRISPR-associated protein 13 (Cas13) was initially found in bacteria. The Cas enzyme contains two higher eukaryote and prokaryote nucleotide-binding domains associated with ribonucleases [1,2,3,4,5]. Since Cas was identified, it has exhibited great potential to be utilized as an RNA-guided RNA-targeting CRISPR-Cas effector. More and more studies have explored the use of the CRISPR-Cas system in the field of therapeutic agents, including neurological disease [6,7], cancer treatment [8], and antiviral drug development in infectious diseases [9]. If this system was to be used as a tool for RNA manipulation in a therapeutic setting, it is essential that no cellular toxic effects occur
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