Lipid-168|Lipid168|Ionizable Lipid for LNP

Cas No.:
Chemical Name:	Lipid-168
Synonyms:	Lipid 168， Lipid168
SMILES:	CCCCCCCCCNC(=O)C(CCCCCCCCC(=O)OCC(CCCC)CCCCCC)N(CCCN(CC)CC)C(=O)CCCCCCCC(=O)OCC(CCCC)CCCCCC
Formula:	C₆₀H₁₁₇O₆N₃
M.Wt:	975.89
Purity:	>95%
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO
Publication:	In vivo genome editing of human haematopoietic stem cells for treatment of blood disorders using mRNA delivery-Saijuan Xu, Dan Liang etl. Nature Biomedical Engineering (2025)

Description:

Lipid168 is an ionizable lipid nanoparticle (LNP) optimized for in vivo mRNA delivery to human hematopoietic stem cells (HSCs). Designed through systematic structural modifications of head and tail groups in Library A, Lipid-168 demonstrated superior bone marrow (BM) targeting efficiency compared to prior candidates (e.g., LNP-028). When encapsulating ABE8e mRNA and sgRNA targeting the HBG promoter (LNP 168-ABE8e-HBG), it achieved 42.6% base editing efficiency in transfusion-dependent β-thalassemia (TDT) patient-derived HSCs engrafted in NCG-X mice, restoring γ-globin expression and globin chain balance in erythroid cells. To mitigate liver tropism, miR-122T sequences were incorporated into the mRNA 3’UTR, reducing hepatic editing from 71% to 19% while maintaining BM efficacy. In Ai14 mice, LNP-168-Cre-miR-122T mediated efficient tdTomato activation in BM cell subsets, including multipotent progenitors (80% editing). Proteomic analysis revealed a unique protein corona enriched with albumin, fibronectin, and fibrinogen, potentially enhancing BM targeting. Safety assessments showed transient inflammatory cytokine spikes (e.g., TNF-α, IL-6) and liver enzyme elevations post-injection, resolving within 48 hours without cumulative toxicity or anti-Cas9/PEG antibodies. Lipid-168 represents a promising non-viral platform for in vivo HSC editing, enabling one-time treatment of blood disorders without cell mobilization or preconditioning.

References:

In vivo genome editing of human haematopoietic stem cells for treatment of blood disorders using mRNA delivery-Saijuan Xu, Dan Liang etl. Nature Biomedical Engineering (2025)

Cat. No.	Product name	Field of application
DC60683	Lipid-168	LIPID168(pKa ~6.5) is an optimized ionizable lipid engineered for in vivo mRNA delivery to hematopoietic stem cells (HSCs) in bone marrow. Developed by Yoltech Therapeutics through high-throughput screening of lipid libraries, it features a diethylamino head group and a tailored hydrophobic tail structure that enables antibody-free targeting. When Lipid 168 was formulated into lipid nanoparticles (LNPs), it achieved 48.5% base editing efficiency in bone marrow cells —surpassing benchmarks like LIPID-028 (19.7%)—and reduced off-target liver editing from 71% to 19% by incorporating miR-122 target sequences. In humanized β-thalassemia models, LNP 168 delivered ABE8e mRNA/sgRNA to patient-derived HSCs, yielding 42.6% editing at the HBG promoter, reactivating fetal hemoglobin (γ-globin) and rescuing erythroid defects . Its bone marrow specificity is driven by a unique protein corona enriched in albumin, fibronectin, and fibrinogen . Safety studies confirmed transient immune responses and no cumulative toxicity . LIPID-168 represents a promising non-viral platform for curative gene therapies in blood disorders.