Description:
Lipid 10a-26 is an ionizable lipid developed by Orna Therapeutics for lipid nanoparticle (LNP) formulations. Lipid 10a-26 is a key ionizable lipid in the LNP-6 formulation. Through structural modification, it exhibits reduced binding to ApoE proteins and lowered liver affinity compared to traditional ionizable lipids. Instead, Lipid 10a-26 demonstrates strong splenic tropism—in non-human primate studies, it effectively delivers payloads to the spleen and immune cells in peripheral blood, such as T cells, NK cells, and macrophages, enabling the possibility of "in vivo CAR-T" therapy. Its pKa is tuned to approximately 6.0–6.5, allowing rapid protonation in the acidic endosomal environment, which promotes endosomal membrane disruption and efficient cytosolic release of circular RNA.
Handling:
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.
Reference:
Circular RNA compositions for targeted and efficient therapeutic protein expression in immune cells for treating cancer or autoimmune disease
By: Wesselhoeft, Alex; Goodman, Brian-WO2021189059 A2 2021-09-23