Lipid-168|Lipid168|Ionizable Lipid for LNP

Cas No.:
Chemical Name:	Lipid-168
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)

MSDS

Cat. No.	Product name	Field of application
DC31000	LP-01	LP-01 is an ionizable cationic amino lipid (pKa = ~6.1). It has been used in the generation of lipid nanoparticles (LNPs). LNPs containing LP-01 and encapsulating both Cas9 mRNA and modified single-guide RNA (sgRNA) for the transport protein transthyretin (Ttr) induce gene editing in liver cells in mice in a dose-dependent manner resulting in reduced serum Ttr levels for at least 12 months.
DC57046	ATX-126(ATX-0126, lipid 10p)	ATX-126(ATX-0126, 10p) is an ionizable cationic lipid (pKa = 6.38).It has been used in the generation of lipid nanoparticles (LNPs) for the delivery of siRNA. Intravenous administration of LNPs containing ATX-126(ATX-0126, 10p) and encapsulating Factor VII siRNA decrease Factor VII blood levels in mice.
DC58046	C12-200	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.
DC42537	ALC-0315	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.
DC52025	SM-102	SM-102 is an ionizable amino lipid that has been used in combination with other lipids in the formation of lipid nanoparticles.Administration of luciferase mRNA in SM-102-containing lipid nanoparticles induces hepatic luciferase expression in mice. Formulations containing SM-102 have been used in the development of lipid nanoparticles for delivery of mRNA-based vaccines.
DC31024	SM-86	SM86 is a cationic, ionizable lipid developed by Moderna as a core component of its lipid nanoparticle (LNP) platform for mRNA therapeutic delivery.SM-086 is structurally optimized and analogous to SM-102 (used in Moderna’s COVID-19 vaccines), with modifications aimed at enhancing mRNA delivery efficiency and safety.SM-86 serves as the primary cationic lipid in three investigational mRNA therapies targeting rare metabolic disorders:mRNA-3927: Restores propionyl-CoA carboxylase activity in propionic acidemia (PA). mRNA-3705: Delivers methylmalonyl-CoA mutase mRNA for methylmalonic acidemia (MMA). mRNA-3210: Provides phenylalanine hydroxylase mRNA to treat phenylketonuria (PKU).
DC57100	Acuitas Lipid A9	Lipid A9 is an ionizable cationic lipid (pKa = 6.27) that has been used in the generation of lipid nanoparticles (LNPs) for the delivery of mRNA and siRNA in vivo. LNPs containing lipid A9 and encapsulating non-stimulatory siRNA increase plasma levels of chemokine (C-C motif) ligand 2 (CCL2), indicating activation of the innate immune response, and decrease body weight in mice.
DC67546	ALC-0307	ALC 0307 is an ionizable amino lipid developed by Acuitas Therapeutics, serving as the critical functional component in lipid nanoparticles (LNPs) for targeted therapeutic delivery. As the core cationic lipid in specific LNP formulations (e.g., k-abe for CPS1-Q335X correction), its key feature is pH-dependent chargeability: it remains neutral at physiological pH but becomes positively charged in acidic environments like endosomes. This property enables efficient encapsulation of nucleic acid payloads (>97% efficiency, e.g., base editor mRNA/gRNA complexes) and facilitates endosomal escape via membrane disruption post-cellular uptake. Its optimized structure promotes selective hepatocyte targeting by binding endogenous apolipoprotein E (ApoE), which subsequently interacts with LDL receptors on liver cells. Preclinical studies show rapid clearance (>99.5% plasma reduction in 14 days) and manageable transient toxicity (mild, reversible cytoplasmic vacuolation in hepatocytes, short-term ALT/AST elevation). LNPs containing ALC0307, alongside helper lipids (cholesterol, DSPC, and PEG-lipid ALC-0159), form stable ~73 nm particles with low polydispersity. This combination enables repeatable, liver-directed delivery of gene editing therapeutics with minimized off-target effects, underpinning its use in individualized in vivo gene correction therapies.
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.
DC60478	ALC-0366	ALC 0366 is an ionizable cationic lipid (pKa = 6.25) from Biontech,which is derived from ALC-0315. ALC0366 has been used as a key component of LNP to deliver BNT142, a lipid nanoparticle (LNP)-formulated RNA (RNA-LNP) encoding a T cell-engaging bispecific antibody that monovalently binds the T cell marker CD3 and bivalently binds claudin 6 (CLDN6), an oncofetal antigen that is absent from normal adult tissue but expressed on various solid tumors.