Integrating Combinatorial Lipid Nanoparticle and Chemically Modified Protein for Intracellular Delivery and Genome Editing

• DOI: 10.1021/acs.accounts.8b00493
• Publication Date: 2018-12-26T20:10:10Z
• Authors: Jin Chang; Xianghan Chen; Zachary Glass; Feng Gao; Lanqun Mao; Ming Wang; Qiaobing Xu
• Keywords: Gene Editing; Drug Carriers; Gene Transfer Techniques; Proteins; 02 engineering and technology; Lipids; Rats; 3. Good health; Mice; CRISPR-Associated Protein 9; Cell Line, Tumor; Animals; Humans; Nanoparticles; CRISPR-Cas Systems; 0210 nano-technology

ConspectusThe use of protein to precisely manipulate cell signaling is an effective approach for controlling fate and developing precision medicine. More recently, programmable nucleases, such as CRISPR/Cas9, have shown extremely high potency editing genetic flow mammalian cells, treating disorders. The therapeutic potential proteins with intracellular target, however, mostly challenged by their low impermeability. Therefore, a delivery system transport the site action in spatiotemporal controlled manner great importance expand index protein.In this Account, we first summarize our most recent advances designing combinatorial lipid nanoparticles diverse chemical structures delivery. By parallel Michael addition or ring-opening reaction aliphatic amines, generated library cationic lipids, identified several leading nanoparticle formulations both vitro vivo. Moreover, optimized structure lipids control degradation release inside cells CRISPR/Cas9 genome-editing delivery.In second part survey endeavor modify protein, particular, coupled platform, improve targeted diseases treatment genome editing. Chemical modification useful tool modulate function drugs. Herein, on approaches following unique findings: (1) chemically modified shows selective turn-on activity based specific microenvironment, which were able protein-based cancer therapy; (2) conjugation hyaluronic acid (HA) allows surface receptor-targeted protein; (3) introduction nonpeptidic boronic into enabled nucleus delivery; report that signal can direct subcellular compartment; (4) fusion negatively supercharged green fluorescent (GFP) facilitates self-assembly delivery.At end give perspective expanding chemistry could be integrated design biocompatible nanocarriers vivo, well harness live treatment.