D-Lin-MC3-DMA(MC3) is the most potent cationic lipid that has been synthesized for Lipid nanoparticles (LNPs) to deliver the siRNA.

Explore lipid formulations evaluated for ocular RNA delivery. Study summaries identify the administration setting and responsive ocular cell populations, including limited-expression results.

| Lipid | Study context | Source & details |
|---|---|---|
| Limited ocular expression | ||
| DLin-MC3-DMA DC10800 | Intravitreal DLin-MC3-DMA was studied in ocular RNA-delivery experiments. In vivo mRNA expression was restricted mainly to the optic-nerve-head region and a few Müller glia; self-amplifying-RNA expression was nearly absent. | [1] Source Primary abstract: in vivo expression limitations |
| C12-200 DC58046 | Intravitreal C12-200 was studied in ocular RNA-delivery experiments. In vivo mRNA expression was restricted mainly to the optic-nerve-head region and a few Müller glia; self-amplifying-RNA expression was nearly absent. | [1] Source Primary abstract: in vivo expression limitations |
| S-Ac7-DOG DC67563 | Intravitreal S-Ac7-DOG was studied in ocular RNA-delivery experiments. In vivo mRNA expression was restricted mainly to the optic-nerve-head region and a few Müller glia; self-amplifying-RNA expression was nearly absent. | [1] Source Primary abstract: in vivo expression limitations |
| In vitro retinal-cell benchmark | ||
| ALC-0315 DC42537 | Retinal-cell culture ALC-0315-F0 was a comparator for EGFP expression in cultured human retinal microvascular endothelial cells. This result does not establish in vivo ocular targeting. | [2] Source Figure 1H; comparator EGFP-positive cells |
| Retinal endothelial-cell research | ||
| Lipid M3 DC68138 | Retinal-cell culture; intravitreal M3-F4 formulations delivered editing cargo to human retinal endothelial cells. The study also evaluated an intravitreal formulation in retinal-disease mouse models. | [2] Source Abstract; Figures 1 and 3; retinal-disease results |
Each entry identifies the reported lipid or complete formulation, experimental setting and source. Reference products and limited-expression findings are labeled in their study context.
D-Lin-MC3-DMA(MC3) is the most potent cationic lipid that has been synthesized for Lipid nanoparticles (LNPs) to deliver the siRNA.

ALC-0315 is an ionisable aminolipid that used for mRNA compaction and aids mRNA cellular delivery. ALC-0315 can be used to form lipid nanoparticle (LNP) delivery vehicles.

C12-200 is a well-known cationic lipid used in the formulation of lipid nanoparticles (LNPs) for the delivery of therapeutic nucleic acids, including siRNA, mRNA, and CRISPR components. It is widely recognized for its high in vivo potency at low doses and is often used as a positive control ionizable lipid in research exploring new ionizable lipids.

S-Ac7-DOg is an ionizable lipid engineered for optimized mRNA delivery to the retina, featuring a sulfur-based ester bond (S-Ac) and dual oleyl glyceride chains (DOg). Its pKa (~6.74) is finely tuned to enhance endosomal escape in acidic environments, enabling efficient cytosolic mRNA release. Unlike traditional lipids (e.g., C12-200, MC3), S-Ac7-DOg incorporates biodegradable ester linkages that hydrolyze intracellularly, minimizing lipid accumulation and reducing innate immune activation. In vitro, S-Ac7-DOg LNPs achieved >80% transfection efficiency in retinal cells (ARPE-19, MIO-M1) with negligible cytokine secretion, outperforming MC3 and rivaling C12-200 while avoiding the latter’s high immunogenicity. In vivo, intravitreal delivery in mice showed robust protein expression in the optic nerve head (ONH) and Müller glia (75–100% of eyes), sustained for ≥7 days. Critically, it induced the lowest immunogenicity among tested lipids: minimal leukocyte infiltration (<1.5-fold vs. PBS), no microglial reactivity, and reduced GFAP upregulation.

Lipid M3 is a novel ionizable lipid. Lipid M3's primary role is to enable the efficient co-encapsulation and delivery of CRISPR/Cas9 components—Cas9 mRNA and sgRNA targeting the VEGFA gene—into human retinal endothelial cells. M3 facilitates critical steps for successful gene editing, including stabilizing the nucleic acid cargo, promoting cellular uptake, and enabling effective endosomal escape to release the payload into the cytoplasm. This results in high gene-editing efficiency (indel frequency ~28.7%). A single intravitreal injection of the M3-F4 LNP carrying this CRISPR system demonstrated potent therapeutic effects in mouse models of diabetic retinopathy by significantly inhibiting pathological neovascularization and vascular leakage, while maintaining excellent biocompatibility.
