Endosomal escape and current obstacles in ionizable lipid nanoparticles mediated gene delivery: lessons from COVID-19 vaccines

Two vaccines based on ionizable lipid nanoparticles achieved significant efficacy during the COVID-19 pandemic.

• The Pfizer/BioNTech Vaccine (BNT162b2) and Moderna Vaccine (mRNA-1273) were developed using ionizable lipid nanoparticles.
• The observed efficacy of these vaccines has spurred increased research into the therapeutic potential of ionizable lipids for various diseases.
• Successful delivery using ionizable lipid nanoparticles depends on selecting appropriate lipids and understanding how they escape endosomes within cells.
• Current knowledge highlights the diversity of lipids and their critical structural and functional features necessary for effective endosomal escape.
• The review includes an analysis of the lipid components in COVID-19 vaccines, linking their chemical properties to immune responses.

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