A Semiconducting Polymer NanoCRISPR for Near-Infrared Photoactivatable Gene Editing and Cancer Gene Therapy

Clustered regularly interspaced short palindromic repeat (CRISPR) gene editing has poor efficacy and off-target side effect concerns. We herein report a semiconducting polymer (SP)-based nanoCRISPR system to improve CRISPR delivery efficacy and allow for near-infrared (NIR) photoactivatable gene editing for cancer therapy. An amphiphilic SP acts as a photothermal converter, and its backbone is grafted with single-stranded deoxyribonucleic acid (DNA), which enables hybridization with single guide ribonucleic acid (sgRNA) via complementary base pairing to form sgRNA/SP-DNA. This sgRNA/SP-DNA nanosystem (nanoCRISPR) can effectively deliver sgRNA into cells and generate heat under NIR laser irradiation via the photothermal effect. The localized heat triggers the dissociation of single-stranded DNA and sgRNA to control the release of sgRNA, thereby achieving precise regulation of CRISPR activity. This NIR photoactivatable gene editing technology is able to precisely regulate the expression of green fluorescent protein (GFP) and polo-like kinase 1 (PLK1) gene for precision gene therapy.