Advances in lipids design for LNP-mediated DNA and RNA delivery
D Zhi, A Halemaimaiti, B Dai, H Li, H Wang, Z Zhang, J Yu, S ZhangDOI 10.1016/j.cis.2026.103897
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This review examines how lipid structure and formulation affect the delivery of DNA, mRNA and siRNA by lipid nanoparticles, while assessing tissue targeting, safety and clinical translation challenges.
Purpose: Improving non-viral nucleic acid delivery depends on matching lipid chemistry to tissue targeting, tolerability and manufacture.
Approach: A literature review of lipid nanoparticle structure–activity relationships, mechanisms and therapeutic applications; not a new clinical trial.
Key findings: The authors discuss ionisable and biodegradable lipids, selective organ targeting (SORT), and applications from gene silencing to mRNA vaccines. They highlight targeting specificity, long-term biocompatibility, scalable production and regulation as unresolved barriers.
Interpretation: Lipid design and formulation need to be considered together when developing next-generation gene therapies.
Limitations: A review of published work does not establish clinical efficacy for any newly proposed formulation.
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