Efficient and durable gene delivery of self complementary adeno-associated virus 6 vector and impact of pre-existing immunity / 生物医学工程学杂志
Journal of Biomedical Engineering
;
(6): 1150-1155, 2012.
Article
in Chinese
| WPRIM
| ID: wpr-246490
ABSTRACT
Recombinant adeno-associated viral (rAAV) vectors are promising vectors for human gene therapy. However, AAV-mediated gene transduction can be hampered because of the pre-existing neutralized natural antibodies (NAbs) in primates. We evaluated transduction efficiency of rAAV6 expressing human alpha-1-anti-trypsin (hAAT) vectors in murine models, and found that these vectors showed stable and high levels of transgene expression. Fluorescence imaging showed that AAV6 expressing enhanced green fluorescent protein (eGFP) by intravenous administration predominantly targeted the liver, but led to self-limited hepatitis. Besides, our study evaluated epidemiology of anti-AAV6 NAb in non-human primates (NHPs) by NAb assay in vitro. The result indicated that 52.17% of NHPs had detectable NAb at 15 dilution rate. In vivo passive transfer experiment showed that AAV6 specific neutralizing antibody, even though with low NAb titer, could significantly inhibit rAAV6 transduction.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Mice, Transgenic
/
Genetic Therapy
/
Alpha 1-Antitrypsin
/
Gene Transfer Techniques
/
Dependovirus
/
Adoptive Transfer
/
Green Fluorescent Proteins
/
Allergy and Immunology
/
Antibodies, Neutralizing
/
Genetic Vectors
Limits:
Animals
Language:
Chinese
Journal:
Journal of Biomedical Engineering
Year:
2012
Type:
Article
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