GVS-18-B6 is a silicon ether-based ionizable lipid developed by Genevant, optimized for mRNA-LNP delivery, characterized by a short-chain trialkyl structure with three C10 alkyl chains (including a cis double bond) and a dimethylamino (DMA) head group linked via a 4-carbon spacer (pKa ~6.15). Its LNP formulations exhibit a narrow particle size distribution (89 nm, PDI=0.06), high mRNA encapsulation efficiency (90%), and pH-dependent surface charge (−0.11 mV at pH 7.5 vs. +2.69 mV at pH 5.5), facilitating endosomal escape. ​​In vivo​​, GVS-18-B6 demonstrated superior liver-specific mRNA expression (5.30×10⁷ pg EGFP/g liver, 2.6× higher than MC3) with minimal spleen accumulation (liver/spleen ratio 92:1 vs. MC3’s 10:1), attributed to rapid non-enzymatic hydrolysis of its silicon ether bonds. This mechanism enables near-complete hepatic clearance within 6 hours in mice and 24 hours in NHPs, avoiding long-term organ retention (MC3 retained 25% in liver after 28 days). Compared to benchmarks (MC3, SM-102, LP-01), GVS-18-B6 showed enhanced potency in RBC hemolysis assays (pH 6.2), indicating earlier endosomal membrane disruption, and maintained stability through 12-month frozen storage or repeated freeze-thaw cycles. ​​Toxicity profiling​​ revealed minimal immunogenicity (MCP-1 levels 0.58×10⁶ vs. MC3’s 1.10×10⁶) and no ALT/AST elevation or anti-PEG antibody induction in NHPs after repeated dosing. Its species-agnostic clearance, low off-target effects, and high tolerability (6 mg/kg dose in mice) position GVS-18-B6 as a leading candidate for chronic disease therapies requiring frequent mRNA administration.

Providing storage is as stated on the product vial and the vial is kept tightly sealed, the product can be stored for up to 24 months.
Wherever possible, you should prepare and use solutions on the same day. However, if you need to make up stock solutions in advance, we recommend that you store the solution as aliquots in tightly sealed vials at -20°C. Generally, these will be useable for up to one month. Before use, and prior to opening the vial we recommend that you allow your product to equilibrate to room temperature for at least 1 hour.

Silicon Ether Ionizable Lipids Enable Potent mRNA Lipid Nanoparticles with Rapid Tissue Clearance-ACS Nano-Apr 3, 2024-by Richard HollandKieu, James Heyes