Rational design of lipid nanoparticles for enabling gene therapies
Ca Brimacombe, Ja Kulkarni, Mhy Cheng, K An, D Witzigmann, Pr CullisDOI 10.1016/j.omtm.2025.101518
Summary
A review of the physical principles and development history behind siRNA lipid nanoparticles for liver gene silencing and mRNA lipid nanoparticles for protein expression.
Purpose: Effective RNA therapies depend on rational carrier design as well as the choice of therapeutic sequence.
Approach: The authors synthesize decades of lipid membrane and drug-delivery research, focusing on LNP formulations already used for siRNA and mRNA.
Key findings: The review links lipid physical properties to liver-directed siRNA gene silencing and mRNA protein expression, and argues that rapid design and manufacture may support more personalized therapies.
Interpretation: Established lipid design principles provide a starting point for further gene therapy modalities.
Limitations: Potential applicability to most gene therapies is an expectation, not evidence of clinical efficacy across diseases.
Related articles
Advances in Colloid and Interface Science
Advances in lipids design for LNP-mediated DNA and RNA delivery
BioDrugsRecent Developments in Lipid Nanoparticle-Mediated Delivery of Biotherapeutics and Gene Therapy Across the Blood-Brain Barrier
SmallRecent Advances in Lipid Nanoparticles: Nucleic Acid Therapeutics and Targeting Strategies
Let's engineer the next delivery breakthrough together
We co-develop nanocarrier and biosensing programs with pharma, biotech and academic groups — from target selection through GMP supply.