The 60-year evolution of lipid nanoparticles for nucleic acid delivery
Pr Cullis, Pl FelgnerDOI 10.1038/s41573-024-00977-6
Summary
This historical review traces lipid-based gene delivery from cationic lipoplexes to ionizable lipid nanoparticles, connecting foundational research with approved mRNA vaccines and siRNA therapy.
Keywords
Purpose: Transporting nucleic acids into cells in vivo has been a longstanding barrier to gene therapy.
Approach: A historical review of two major research paths: cationic lipoplexes and ionizable cationic lipid nanoparticles.
Key findings: The authors connect decades of lipid-delivery research to approved mRNA vaccines and patisiran, an siRNA treatment for hereditary transthyretin amyloidosis. Additional LNP-enabled therapies are under development.
Interpretation: Lessons from these two development paths inform the design of future nucleic acid carriers.
Limitations: Historical success with particular products does not guarantee success for other cargos or tissues.
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