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
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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 synthesise 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 personalised 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.
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