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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Pardridge, William M. |
| Abstract | Nonviral plasmid DNA is delivered to the brain via a transvascular route across the blood-brain barrier (BBB) following intravenous administration of DNA encapsulated within Trojan horse liposomes (THLs), also called PEGylated immunoliposomes (PILs). The liposome surface is covered with several thousand strands of polymer (e.g., polyethylene glycol [PEG]), and the tips of 1%-2% of the polymer strands are conjugated with a targeting monoclonal antibody that acts as a molecular Trojan horse (MTH). The MTH binds to a receptor (e.g., for transferrin or insulin) on the BBB and brain cell membrane, triggering receptor-mediated transcytosis of the THL across the BBB in vivo, and receptor-mediated endocytosis into brain cells beyond the BBB. The persistence of transgene expression in the brain is inversely related to the rate of degradation of the episomal plasmid DNA. THL technology enables an exogenous gene to be widely expressed in the majority of cells in adult brain (or other organs) within 1 d of a single intravenous administration. Applications of the THLs include tissue-specific gene expression with tissue-specific promoters, complete normalization of striatal tyrosine hydroxylase in experimental Parkinson's disease following intravenous tyrosine hydroxylase gene therapy, a 100% increase in survival time of mice with brain tumors following weekly intravenous antisense gene therapy using THLs, and a 90% increase in survival time with weekly intravenous RNA interference (RNAi) gene therapy in mice with intracranial brain tumors. This protocol describes the preparation of THLs for use in gene transfer in vitro or in vivo. |
| File Format | HTM / HTML |
| ISSN | 19403402 |
| Issue Number | 4 |
| Volume Number | 2010 |
| e-ISSN | 15596095 |
| Journal | Cold Spring Harbor Protocols |
| Language | English |
| Publisher | Cold Spring Harbor Laboratory Press |
| Publisher Date | 2010-04-01 |
| Publisher Place | United States |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Discipline Clinical Laboratory Techniques Blood-brain Barrier Metabolism Gene Transfer Techniques Genetic Therapy Methods Liposomes Animals Endocytosis Mice Transformation, Genetic Journal Article Research Support, N.i.h., Extramural Research Support, U.s. Gov't, Non-p.h.s. |
| Content Type | Text |
| Resource Type | Article |
| Subject | Biochemistry, Genetics and Molecular Biology |
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