mRNA?Loaded Lipid?Like Nanoparticles for Liver Base Editing Via the Optimization of Central Composite Design

Messenger RNA (mRNA) has come into the spotlight due to its potential for addressing a staggering number of diseases, while lack effective and safe carriers in vivo delivery significantly limits clinical application. Herein, lipid-like nanoparticles (LLNs) containing three new cholesterol derivatives achieve liver targeting mRNA is investigated. The central composite design (CCD) used tailor formulation LLNs through optimization molar ratios these required targeting. optimized (O-LLNs) are able systemically deliver mice with synergistic action prolonged systemic circulation, increased targeting, enhanced hepatocyte uptake. O-LLNs outperformed DLin-MC3-DMA (MC3) functional Cre-recombinase (Cre) human erythropoietin (hEPO) mRNA. Successful cytidine base editor (CBE mRNA) sgRNA by achieved more than 8% correction rates liver-related metabolism disorder, phenylketonuria (PKU). In conclusion, general method above can accelerate screening multicomponent nanoparticle formulations, ones demonstrate great as vehicles targeted gene therapy specific tissues.