Transcription activator-like effector base editing delivered by a targeted lipid nanoparticle for therapy of lung cancer.
TL;DR
A transcription activator-like effector (TALE) base editor that can accurately identify KRAS gene under the guide of TALE and sgRNA, convert C base to T base and generate a stop codon and blocking the expression of KRAS is reported.
Abstract
Lung cancer is the leading cause of cancer-related deaths worldwide. Among them, non-small cell lung cancer (NSCLC) accounts for approximately 85% of all cases, while the mutation of KRAS oncogene plays a crucial role in its formation and metastasis. Here, we report a transcription activator-like effector (TALE) base editor that can accurately identify KRAS gene under the guide of TALE and sgRNA, convert C base to T base, thereby generating a stop codon and blocking the expression of KRAS. Besides, a targeted TALE base editing lipid nanoparticle (targeted TALE LNP) is developed by rationally designing with cancer-targeted EGFR peptide. The targeted TALE LNP exhibits a base editing effect, cancer targeting, and remarkable therapy efficacy in NSCLC cancer-bearing mice. In conclusion, the targeted TALE LNP has the potential to treat lung cancer with KRAS gene mutation through an approach of transcription activator-like effector base editing.
