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Development of the dodecahedral penton particle from adenovirus 3 for therapeutic application

P. Fuschiotti^1,

J. F. Conway^1,

¹ Laboratoire de Microscopie Electronique Structurale, Institut de Biologie Structurale, UMR 5075 CNRS-CEA-UJF, F-38027 Grenoble cedex, France
² Laboratoire d'Enzymologie Moléculaire, Institut de Biologie Structurale, UMR 5075 CNRS-CEA-UJF, F-38027 Grenoble cedex, France
³ Institut de Virologie Moléculaire et Structurale, FRE 2854 CNRS-UJF, BP181, F-38042 Grenoble cedex 9, France

Correspondence
J. F. Conway
jxc100{at}pitt.edu

The subviral dodecahedral particle of adenovirus 3, which assembles spontaneously in insect cells expressing the viral penton base protein, shows promise as a vector for drug delivery. Its ability to gain cell entry has been demonstrated and recent structural analysis has outlined details of the interfaces between penton bases and the importance of proteolysis of the penton base N terminus for assembly, providing a basis for understanding particle assembly and stability. Here, work in manipulating the assembly status of the dodecahedron by changing buffer conditions and subsequent success in passively encapsidating a marker molecule is described. This represents an important stage towards development of the dodecahedral particle for use as a delivery vehicle capable of targeting therapeutic molecules to specific cell types.

Present address: Department of Immunology, University of Pittsburgh School of Medicine, W1052 Biomedical Science Tower, 200 Lothrop Street, Pittsburgh, PA 15261, USA.

Present address: Department of Structural Biology, University of Pittsburgh School of Medicine, Room 2047, Biomedical Science Tower 3, 3501 Fifth Avenue, Pittsburgh, PA 15260, USA.