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Updated: Apr 4, 2026
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Formulating and Characterizing Lipid Nanoparticles for Gene Delivery using a Microfluidic Mixing Platform
Published on: February 25, 2021
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Formulation Screening of Lipid Nanoparticles Enhances mRNA Delivery to Retina
Jin Yu1,2, Zesen Ma3, Haiyang Tong2,4
1Institutes of Physical Science and Information Technology, Anhui University, Hefei, Anhui 230601, China.
Molecular Pharmaceutics
|April 3, 2026
Summary
Optimized lipid nanoparticles (LNPs) show enhanced delivery of mRNA for treating inherited retinal diseases (IRDs). Formulation B11 significantly improves reporter gene expression in retinal tissues compared to existing methods.
Area of Science:
- Ophthalmology
- Gene Therapy
- Nanomedicine
Background:
- Inherited retinal diseases (IRDs) cause progressive vision loss and are genetically diverse.
- Adeno-associated virus (AAV) vectors are used for IRD gene therapy but have limitations like packaging capacity and toxicity.
- Lipid nanoparticles (LNPs) are effective nonviral vectors for nucleic acid delivery, but their formulation parameters require systematic optimization for ocular applications.
Purpose of the Study:
- To systematically optimize lipid nanoparticle (LNP) formulations for ocular delivery of nucleic acid therapeutics.
- To identify an LNP formulation that enhances mRNA delivery and gene expression in retinal tissues.
- To evaluate the efficacy and mechanism of optimized LNPs for treating inherited retinal diseases.
Main Methods:
- Employed a design of experiments strategy to create and screen LNP libraries for ocular delivery.
- Compared the efficacy of different LNP formulations, including B11, SM-102, and MC3, for reporter gene expression in vivo.
- Investigated the cellular uptake mechanisms of LNP B11 and assessed its ability to mediate functional protein expression in retinal tissue.
Main Results:
- Identified LNP formulation B11, which demonstrated 2.6-fold and 3.0-fold higher reporter gene expression in vivo compared to SM-102 and MC3.
- Mechanistic studies showed LNP B11 is internalized via caveolae-mediated endocytosis and macropinocytosis.
- LNP B11 effectively delivered Cre mRNA to induce gene expression in the retinal pigment epithelium and improved functional protein expression in reporter mice.
Conclusions:
- LNP formulation B11 represents a highly promising optimized LNP for retinal mRNA delivery.
- Systematic optimization of LNP formulation parameters is crucial for advancing nucleic acid therapeutics for retinal diseases.
- The findings support the potential of LNP-based mRNA delivery as a viable strategy for treating inherited retinal diseases.
