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 (NB2), 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 (FNB2) integrates optimized cryoprotectants and a surface-engineered nanoparticle design, preserving morphology and function without excessive excipients. 

FNB2 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. 

FNB2 represents a scalable and robust platform for genetic therapeutics, vaccines, and biologics, particularly well-suited for resource-limited and emergency medical applications.

Adv Mater. 2026 Mar 12:e10532.

https://advanced.onlinelibrary.wiley.com/doi/10.1002/adma.202510532