| 학회 | 한국고분자학회 |
| 학술대회 | 2005년 가을 (10/13 ~ 10/14, 제주 ICC) |
| 권호 | 30권 2호 |
| 발표분야 | 의료용 고분자 부문위원회 |
| 제목 | Regulation of transduction efficiency by pegylation of baculovirus vector in vitro and in vivo |
| 초록 | Gene therapy has the potential to treat devastating inherited diseases for which there is little hope of finding a conventional cure and is a method for the prevention, correction or modulation of genetic and acquired diseases that uses genes to therapeutic proteins. Traditionally, gene therapy systems have been classified as viral vector-mediated systems and non-viral vector-mediated systems. Currently, because of their highly evolved and specialized components, viral systems are by far the most effective means of gene delivery and achieve high efficiencies for both delivery and expression. In fact, around 75% of recent clinical protocols involving gene therapy use recombinant virus-based vectors for gene delivery. As yet, however, no definitive evidence has been presented for the clinical effectiveness of any gene therapy protocol. Although viral systems are potentially very efficient, the weakness of current methodology is attributable to the limitations of viral-mediated delivery, including toxicity, restricted targeting of specific cell types, limited DNA carrying capacity, production and packaging problems, recombination, and high cost. On the other hand, the use of non-viral gene therapy vectors has been hampered by low level of transfection efficiency and lack of sustained gene expression. Covalent modification of proteins and enzymes with activated poly(ethylene glycol) (PEG) has been extensively studied. PEG is expected to be a good candidate for the hydrophilic part due to the high solubility in water, low cytotoxicity, and enhanced cell permeability. PEG-modified proteins have been proved to have increased plasma half-lives and stability and reduced immunogenicity in vivo. Recently an approach, where PEG is conjugated onto the viral capsid, has been investigated for reducing the immune response against adenovirus. The baculovirus Autographa californica multiple nuclear polyhedrosis virus (AcMNPV) has been used widely for high-level expression of recombinant proteins in insect cells and mammalian cells because it has several advantages such as undetectable cytopathic effect, non-replication nature, large insertion capacity and low cytotoxicity. Moreover, recombinant baculovirus vectors engineered to contain mammalian cell-active promoter elements have been applied to the delivery of genes into mammalian cells, such as hepatocytes, neurons, etc. The non-specific electrostatic charge interaction between virus envelope and mainly heparan sulfate proteoglycan on the host cell membrane is probably the initiating step of virus binding, and baculovirus will enter mammalian cells via electrostatic interaction-mediated endocytosis. This non-specific and rapid interaction between baculovirus and cells might be a drawback to the development of tissue-targeting gene carrier following in vivo intravenous injection. In previous studies, it was found that complement destroys the ability of virus to transfer genes in vivo and inactivation of baculovirus in human serum and whole blood was prevented by treatment with cobra venom factor. In this study, A549 cells were infected with pegylated baculovirus containing GFP gene. Also, BALB/c mice were inoculated with pegylated baculovirus containing GFP gene. In conclusion, transduction efficiency was regulated by pegylation of baculovirus vector in vitro and in vivo. These results might make the potential of the development of tissue-specific baculvirus vector system plausible. |
| 저자 | 김유경, 박인규, 최재영, 제연호, 김화, 김현우, 조명행, 조종수 |
| 소속 | 서울대 |
| 키워드 | Baculovirus; Pegylation; tissue-specific targeting; Gene delivery |
