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Tuning Lipid Nanoparticles for RNA Delivery to Extrahepatic Organs
Donghui Song1, Yu Zhao1, Zeyu Wang1
1Department of Biomedical Engineering, Tufts University, Medford, MA, 02155, USA.
Advanced Materials (Deerfield Beach, Fla.)
|September 5, 2024
Summary
Researchers are developing lipid nanoparticles (LNPs) to deliver RNA therapeutics beyond the liver. Strategies focus on modifying LNP composition and ionizable lipids to achieve organ-selective delivery for broader therapeutic applications.
Area of Science:
- Biotechnology
- Nanomedicine
- Drug Delivery Systems
Background:
- RNA therapeutics show clinical promise but face delivery challenges.
- Lipid nanoparticles (LNPs) are common nonviral vectors for RNA, but often accumulate in the liver.
- Targeting organs beyond the liver is crucial for expanding LNP-based RNA therapeutic applications.
Purpose of the Study:
- To review strategies for designing LNPs for extrahepatic RNA delivery.
- To discuss how LNP formulation and ionizable lipid modification influence organ targeting.
- To provide an outlook on next-generation LNP delivery platforms.
Main Methods:
- Altering LNP formulation composition.
- Chemically modifying ionizable lipid components.
- Analyzing changes in physicochemical properties and biomolecular corona formation.
Main Results:
- LNP formulation and ionizable lipid modifications alter physicochemical properties.
- Changes in LNPs affect biomolecular corona composition, mediating organ selectivity.
- Successful strategies enable RNA delivery to organs beyond the liver.
Conclusions:
- Modifying LNP formulation and ionizable lipids are effective strategies for extrahepatic RNA delivery.
- The biomolecular corona plays a key role in mediating organ-selective LNP delivery.
- Future LNP platforms should focus on cell-type targeting, safety, and overcoming physiological barriers.
