發展肝細胞專一性的蛋白微脂體複合物以作為肝臟基因治療的載體
Date Issued
2001
Date
2001
Author(s)
倪衍玄
DOI
892314B002386
Abstract
Background/Aim: Asiaologlycoprotein (AsG)
receptors uniquely exist in hepatocytes.
Protamine is a polyarginine and able to condense
DNA. Liposome is widely used as a gene
transfer vector. In this study, we designed a new
complex containing AsG-protamine conjugate
and mixed with liposome, which uses AsG as a
liver specific ligand, protamine to condense
DNA, and both protamine and liposome to carry
foreign DNA to form an efficient hepatic gene
transfer vector.
Methods: Conjugation reaction of AsG and
protamine and liposome was monitored by
capillary electrophoresis. The product then
carried green fluorescent protein (GFP) gene to
transfect human hepatoma cell line and
non-hepatocyte cell line to demonstrate its
efficacy and specificity in vitro. For the in vivo
study, this gene transfer complex carried GFP
gene and injected into the mice either through
tail veins or portal veins. The expression of GFP
was assayed 48 hours later by the direct
fluorescent microscopic examinations and the
flow cytometry.
Results: AsG-protamine conjugate and liposome
mixture had a 2 and 10 more folds increase of
GFP expression than liposome or conjugate
alone in hepatoma cell line respectively.
However, the in vivo studies showed the gene
expression level in the liver was minimal either
through tail veins or portal veins.
Conclusion: AsG-protamine conjugate and
liposome mixture is a new liver-specific gene
transfer vector. This vector may work well in ex
vivo gene therapy and needs further modification
to apply to in vivo hepatic gene therapy.
Subjects
asialoglycoprotein
protamine
liposome
gene therapy
Publisher
臺北市：國立臺灣大學醫學院小兒科
Type
report
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