Anti-PEG Immunity upon nucleic acid delivery

对于pDNA和siRNA的体内使用，经常使用PEG对脂质体进行表面修饰以实现靶组织中的基因表达或抑制。然而，PEG包被的脂质体诱导抗PEG IgM免疫。在这里，我们研究了Toll样受体（TLR）如何增强抗PEG IgM的产生。在TLR 9 KO小鼠中观察到pDNA-PEG脂质体的抗PEG IgM产生减弱，在TLR 7 KO小鼠中观察到siRNA-PEG脂质体的IgM产生减弱。此外，PG修饰pDNA-PEG脂质体可抑制抗多聚体IgM的产生。在体内实验中，第二剂量的pDNA-PG脂质体恢复了肿瘤组织中的蓄积水平，与第一剂量相当，而第二剂量的pDNA-PEG脂质体的肿瘤蓄积水平显著受损。这些结果可能对设计和开发有效的PEG包被的非病毒核酸递送纳米载体系统具有重要意义。

For in vivo use of pDNA and siRNA, surface modification of the liposome with PEG is frequently applied to achieve gene-expression or suppression in the targeted tissue. However, PEG-coated liposomes induce anti-PEG IgM immunity. Here, we investigated how a Toll-like receptor (TLR) might enhance anti-PEG IgM production. Attenuated anti-PEG IgM production for pDNA-PEG liposome was observed in TLR9 KO mice, the attenuated IgM production for siRNA-PEG liposome was in TLR7 KO mice. In addition, the modification of pDNA-PEG liposome with PG attenuated the production of anti-polymer IgM. In vivo experiment, a second dose of pDNA-PG liposome restored the accumulation level in the tumor tissue, comparable to that of the first dose, whereas the tumor accumulation level of a second dose of pDNA-PEG liposome was significantly compromised. These results may have important implications for the design and development of an efficient PEG-coated non-viral nucleic acid delivery nanocarrier system.