Disclosed herein are novel cationic lipids that can be used in combination with other lipid components such as cholesterol and PEG-lipids to form lipid nanoparticles with oligonucleotides. The cationic lipids can demonstrate enhanced efficacy along with lower liver toxicity as a result of lower lipid levels in the liver. The present invention employs low molecular weight cationic lipids with one short lipid chain coupled with inclusion of hydrolysable functionality in the lipid chains to enhance the efficiency and tolerability of in vivo delivery of siRNA.
本文披露了一种新型阳离子脂质,可与其他脂质组分(如
胆固醇和P
EG-脂质)结合使用,形成与寡核苷酸一起的脂质纳米粒子。这些阳离子脂质可以表现出增强的功效,同时由于肝脏中脂质
水平较低,从而表现出更低的肝毒性。本发明采用低分子量的阳离子脂质,具有一个短脂肪链,同时在脂肪链中包含可
水解的功能,以增强siRNA在体内传递的效率和耐受性。