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.