A10 (Compound 16) is a diketopiperazine‑based ionizable lipid disclosed in WO 2025/217298 A1 (PCT/US2025/023899) developed by NAVA Therapeutics that enables potent, cell‑selective in vivo delivery of mRNA and nucleic acids without targeting ligands. It forms stable, well‑tolerated lipid nanoparticles (LNPs) that preferentially transfect hematopoietic stem cells (HSCs), bone marrow progenitors, lung epithelium, endothelium, and immune cells while minimizing liver off‑target delivery. In both mice and non‑human primates, A10‑containing LNPs drive functional mRNA expression and gene editing in CD34⁺ HSCs at clinically relevant low doses (0.25–1.0 mg/kg), supporting in vivo HSC gene therapy without ex vivo manipulation.

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.