Nanoparticle-Based CRISPR Screen to Identify Genetic Regulators of Chemoresistance
Abstract
Lung cancer is principal cause of cancer death in United States. Although many currently employed treatments are initially effective, the acquisition of chemoresistance in the majority of lung cancer patients frequently leads to eventual patient mortality. Recently, pooled CRISPR/Cas9 screenings strategies have enabled unbiased and massively parallel analysis of molecular determinants. In some cases, the delivery of Cas9 and sgRNA were conducted in vitro, and then followed by in vivo validation to modulate acquired drug resistance in cancer. However, most CRISPR screens have been performed in vitro, and the small number of such screens conducted in vivo have utilized in vitro viral delivery of sgRNA libraries. In such cases, the identified targets are relevant to tumor initiation but may lack relevance to the acquisition or persistence of chemoresistance. In addition, viral delivery lacks specificity in vivo and, if repeated, may demonstrate immunogenicity. Given these unfavorable features, we here propose to use fully in vivo CRISPR screens utilizing lipid-polymer hybrid NPs to a deliver pooled sgRNA libraries into growing chemoresistant tumors in vivo, to identify genes that modulate chemoresistance in a clinically relevant setting. The LCRP Area(s) of Emphasis that will be addressed would be "Identify innovative strategies for the treatment of lung cancer." and "Understand mechanisms of resistance to treatment (primary and secondary)."
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2023
- Accession Number
- AD1224427
Entities
People
- Lufei Sui