Development of the dodecahedral penton particle from adenovirus 3 for therapeutic application.
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.
Fuschiotti
P
P
Laboratoire de Microscopie Electronique Structurale, Institut de Biologie Structurale, UMR 5075 CNRS-CEA-UJF, F-38027 Grenoble cedex, France.
Fender
P
P
Laboratoire d'Enzymologie Moléculaire, Institut de Biologie Structurale, UMR 5075 CNRS-CEA-UJF, F-38027 Grenoble cedex, France.
Schoehn
G
G
Institut de Virologie Moléculaire et Structurale, FRE 2854 CNRS-UJF, BP181, F-38042 Grenoble cedex 9, France.
Conway
J F
JF
Laboratoire de Microscopie Electronique Structurale, Institut de Biologie Structurale, UMR 5075 CNRS-CEA-UJF, F-38027 Grenoble cedex, France.
D000260:Adenoviruses, Human / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D000818:Animals; D002021:Buffers; D036022:Capsid Proteins / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D002460:Cell Line; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D006863:Hydrogen-Ion Concentration; D007313:Insecta; D011487:Protein Conformation; D014162:Transfection / Q000379:methods*
D002021:Buffers; D036022:Capsid Proteins; C043322:penton protein, adenovirus