| Budget Amount *help |
¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000)
Fiscal Year 2013: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2012: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2011: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
|
|---|
| Research Abstract |
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.
|
