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
Summary
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 ionizable 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.
Related articles
BioDrugs
Recent 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
Molecular Therapy Methods & Clinical DevelopmentRational design of lipid nanoparticles for enabling gene therapies
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.