Blood clearance rates of adenovirus type 5 in mice
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作者:
Alemany, R
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Univ Alabama, Div Human Gene Therapy, Wallace Tumor Inst, Birmingham, AL 35294 USAUniv Alabama, Div Human Gene Therapy, Wallace Tumor Inst, Birmingham, AL 35294 USA
Alemany, R
[1
]
Suzuki, K
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Univ Alabama, Div Human Gene Therapy, Wallace Tumor Inst, Birmingham, AL 35294 USAUniv Alabama, Div Human Gene Therapy, Wallace Tumor Inst, Birmingham, AL 35294 USA
Suzuki, K
[1
]
Curiel, DT
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Univ Alabama, Div Human Gene Therapy, Wallace Tumor Inst, Birmingham, AL 35294 USAUniv Alabama, Div Human Gene Therapy, Wallace Tumor Inst, Birmingham, AL 35294 USA
Curiel, DT
[1
]
机构:
[1] Univ Alabama, Div Human Gene Therapy, Wallace Tumor Inst, Birmingham, AL 35294 USA
Persistence of adenovirus type 5 in blood has implications for the pathogenicity of the virus infection and for the use of this virus in oncolysis and gene therapy. In this study, the kinetics of adenovirus clearance from blood in mice has been evaluated. After a single inoculation of concentrated virus into the vena cava, virus half-life was less than 2 min. Depletion of Kupffer cells (KC) resulted in increased viraemia. After tail-vein injection, virus and latex beads co-localized within KIC. An important factor in clearance by KC is the negative charge of particles. Deletion of the hexon hypervariable region 1 acidic stretch decreased the negative charge of the virion but it did not increase blood persistence. Coating with PEG ('PEGylation') reduced the clearance rate but also reduced infectivity.