In Vitro and In Vivo Screening of Lipid Nanoparticles Containing Novel Biodegradable Ionizable Lipids

Supervisor: Prof. Peng George Wang

Ionizable lipids with unsaturated tails, multiple tails, branched tails, and bio-degradable linkages are considered to have potentially higher mRNA delivery efficiency based on structure-activity relationship(SAR) studies of ionizable lipids reported previously.

A library of novel ionizable lipids embodying biodegradable disulfide bonds as well as unsaturated/branched tails was tested in this work. Lipid nanoparticles containing different novel ionizable lipids were manufactured by microfluidic mixers firstly, then prepared FLuc-mRNA LNPs were characterized and screened in vitro and in vivo for mRNA delivery efficiency. Finally, in vivo toxicity of LNPs comprising potent novel ionizable lipids were evaluated. The commercial ionizable lipids SM102, MC3 and ALC0315 were set as references in this work. 

• Preparation and characterization of LNPs containing novel ionizable lipids  

• In vitro and in vivo screening of FLuc-mRNA LNPs 

• In vitro and in vivo toxicity evaluation of LNPs comprising novel ionizable lipids