AAV8 virions hijack serum proteins to increase hepatocyte binding for transduction enhancement

It has been demonstrated that human serum albumin (HSA) directly interacts with AAV virions and enhances AAV transduction. Several other proteins have also been identified a potential for enhancing AAV8 liver transduction. In our study, LDL or transferrin could enhance transduction in vitro and in v...

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Bibliographic Details
Published in:Virology (New York, N.Y.) N.Y.), 2018-05, Vol.518, p.95-102
Main Authors: Pei, Xiaolei, He, Ting, Hall, Nikita E., Gerber, David, Samulski, R. Jude, Li, Chengwen
Format: Article
Language:English
Subjects:
AAV
Animals
Cell Line
Dependovirus - physiology
Gene therapy
Gene Transfer Techniques
Genetic Vectors
Hepatocytes - metabolism
Hepatocytes - virology
Humans
LDL
Mice
Serum protein
Transduction
Transduction, Genetic
Transferrin
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Summary:It has been demonstrated that human serum albumin (HSA) directly interacts with AAV virions and enhances AAV transduction. Several other proteins have also been identified a potential for enhancing AAV8 liver transduction. In our study, LDL or transferrin could enhance transduction in vitro and in vivo. We also found that any combination of two or three of these proteins (HSA, LDL, and transferrin) increased AAV8 transduction in Huh7 cells and in mice liver, which was similar to albumin alone. Pre-incubation of HSA with AAV8 virions prevented AAV8 virions from binding to other proteins. Furthermore, these serum protein receptors didn’t impact AAV8 transduction but blocked the transduction enhancement from AAV8-serum protein complexes. These results indicate that serum proteins are hijacked by AAV8 vectors to increase hepatocyte binding, which shares same binding site. Importantly, the results could help us design an optimal formulation for effective AAV vector delivery in future clinical trials. •Serum proteins, such as albumin, LDL, and transferrin could bind to AAV8 capsid.•Serum albumin, LDL, and transferrin share the same location on capsid when binding to AAV8.•Serum albumin, LDL, and transferrin could enhance AAV8 transduction efficiency both in vitro and in vivo.•Serum proteins couldn’t change the AAV8 tropism in vivo.•AAV8 could hijack serum proteins and bind to their receptors on target tissues, to enhance the transduction efficiency.
ISSN:0042-6822
1096-0341
DOI:10.1016/j.virol.2018.02.007