Traceless photodegradable polymer cocoons for universal protein delivery and light-controlled gene editing

Polymer conjugation was found highly valuable in clinic to improve the bioavailability of protein therapeutics. However, it is still a tremendous challenge to achieve a complete release of original proteins from the conjugated hybrid under external stimulus to recover active proteins in the targeted tissue. Herein, we report a general light-controlled protein delivery methodology by weaving a photodegradable polymer cocoon around proteins, which could reliably protect them from degradation in the dark while efficiently releasing them under illumination without any residual atoms. The surface charge of the polymer shell is easily tunable to facilitate efficient cell uptake. The versatility of this strategy is demonstrated by the delivery of the Cas9/sgRNA complex that realized light-controlled gene editing both in vitro and in vivo, and such repertoire is of particular value in regard to minimizing the off-target toxicity of CRISPR-Cas9-based gene therapy.