A Rationally Designed Semiconducting Polymer Brush for NIR‐II Imaging‐Guided Light‐Triggered Remote Control of CRISPR/Cas9 Genome Editing

Abstract The clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR‐associated protein 9 (Cas9) genome‐editing system has shown great potential in biomedical applications. Although physical approaches, viruses, and some nonviral vectors have been employed for CRISPR/Cas9 delivery and induce some promising genome‐editing efficacy, precise genome editing remains challenging and has not been reported yet. Herein, second near‐infrared window (NIR‐II) imaging‐guided NIR‐light‐triggered remote control of the CRISPR/Cas9 genome‐editing strategy is reported based on a rationally designed semiconducting polymer brush (SPPF). SPPF can not only be a vector to deliver CRISPR/Cas9 cassettes but also controls the endolysosomal escape and payloads release through photothermal conversion under laser irradiation. Upon laser exposure, the nanocomplex of SPPF and CRISPR/Cas9 cassettes induces effective site‐specific precise genome editing both in vitro and in vivo with minimal toxicity. Besides, NIR‐II imaging based on SPPF can also be applied to monitor the in vivo distribution of the genome‐editing system and guide laser irradiation in real time. Thus, this study offers a typical paradigm for NIR‐II imaging‐guided NIR‐light‐triggered remote control of the CRISPR/Cas9 system for precise genome editing. This strategy may open an avenue for CRISPR/Cas9 genome‐editing‐based precise gene therapy in the near future.