A Cryoprotectant‐Compatible Nanoporous Platform for Stable and Scalable Delivery of Biopharmaceuticals

ABSTRACT CRISPR‐Cas9 ribonucleoproteins (RNPs) represent a promising class of biopharmaceuticals for treating genetic and complex diseases. However, their clinical translation is limited by instability during storage and delivery. Lyophilization offers a potential solution, though conventional approaches often compromise structural integrity and bioactivity under non‐cryogenic conditions. Here, we have developed a nanostructured delivery platform, designated Nano Banker & Blowball (NB 2 ), which features a blowball‐like architecture and tunable nanoscale pores. These pores are designed to protect RNPs and enable controlled release. The freeze‐dried formulation (FNB 2 ) integrates optimized cryoprotectants and a surface‐engineered nanoparticle design, preserving morphology and function without excessive excipients. FNB 2 exhibits rapid rehydration and retains ∼70% of gene editing activity post‐lyophilization, enabling robust functional gene editing in vitro and in vivo. It also maintains long‐term stability and supports efficient cellular uptake, enabling administration via multiple routes. FNB 2 represents a scalable and robust platform for genetic therapeutics, vaccines, and biologics, particularly well‐suited for resource‐limited and emergency medical applications.