Anti-PEG Immunity upon nucleic acid delivery
| Project/Area Number |
23390012
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Physical pharmacy
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| Research Institution | The University of Tokushima |
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Principal Investigator |
KIWADA Hiroshi 徳島大学, ヘルスバイオサイエンス研究部, 非常勤講師 (50120184)
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| Co-Investigator(Kenkyū-buntansha) |
ISHIDA Tatsuhiro 徳島大学, 大学院・へルスバイオサイエンス研究部, 教授 (50325271)
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| Project Period (FY) |
2011-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| 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)
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| Keywords | ＤＤＳ / ＰＥＧ / リポソーム / ABC現象 / Anti-PEG IgM / 免疫活性化 / DDS / PEG |
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| 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.
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Report
(4 results)
Research Products
(47 results)
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[Journal Article] The co-delivery of oxaliplatin abrogates the immunogenic response to PEGylated siRNA-lipoplex2013
Author(s)
Alaaeldin, E.,, Abu Lila, A.S., Moriyoshi, N., Sarahan, H.A., Ishida, T., Khaled A. Khale, Kiwada, H
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Journal Title
Pharm. Res
Volume: 30
Issue: 9
Pages: 2344-2354
DOI
Related Report
Peer Reviewed
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[Journal Article] Use of polyglycerol (PG), instead of polyethylene glycol (PEG), prevents induction of the accelerated blood clearance phenomenon against long-circulating liposomes upon repeated administration.2013
Author(s)
Abu Lila, A.S., Nawata, K., Shimizu, T., Ishida, T., Kiwada, H.
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Journal Title
Int. J. Pharm.
Volume: 456
Issue: 1
Pages: 235-242
DOI
Related Report
Peer Reviewed
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[Journal Article] Accelerated blood clearance of PEGylated liposomes containing doxorubicin upon repeated administration to dogs2012
Author(s)
Suzuki, T., Ichihara, M., Hyodo, K., Yamamoto, E., Ishida, T., Kiwada, H., Ishihara, H., Kikuchi, H
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Journal Title
Int. J. Pharm
Volume: 436
Issue: 1-2
Pages: 636-643
DOI
Related Report
Peer Reviewed
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[Presentation] Accelerated blood clearance phenomenon upon PEGylated protein.2013
Author(s)
Mima, Y., Hashimoto, Y., Shimizu, T., Ishida, T., Kiwada, H.,
Organizer
40th Annual Meeting & Exposition of the Controlled Release Society
Place of Presentation
Hawaii Convention Center (USA)
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