Exploiting the natural diversity in adenovirus tropism for therapy and prevention of disease.
Since targeting of recombinant adenovirus vectors to defined cell types in vivo is a major challenge in gene therapy and vaccinology, we explored the natural diversity in human adenovirus tissue tropism. Hereto, we constructed a library of Ad5 vectors carrying fibers from other human serotypes. From this library, we identified vectors that efficiently infect human cells that are important for diverse gene therapy approaches and for induction of immunity. For several medical applications (prenatal diagnosis, artificial bone, vaccination, and cardiovascular disease), we demonstrate the applicability of these novel vectors. In addition, screening cell types derived from different species revealed that cellular receptors for human subgroup B adenoviruses are not conserved between rodents and primates. These results provide a rationale for utilizing elements of human adenovirus serotypes to generate chimeric vectors that improve our knowledge concerning adenovirus biology and widen the therapeutic window for vaccination and many different gene transfer applications.
Havenga
M J E
MJ
Crucell Holland B.V., 2301 CA Leiden, The Netherlands. m.havenga@crucell.com
Lemckert
A A C
AA
Ophorst
O J A E
OJ
van Meijer
M
M
Germeraad
W T V
WT
Grimbergen
J
J
van Den Doel
M A
MA
Vogels
R
R
van Deutekom
J
J
Janson
A A M
AA
de Bruijn
J D
JD
Uytdehaag
F
F
Quax
P H A
PH
Logtenberg
T
T
Mehtali
M
M
Bout
A
A
D000260:Adenoviruses, Human / Q000145:classification* / Q000235:genetics*; D000818:Animals; D001842:Bone and Bones; D002213:Capsid / Q000235:genetics*; D036022:Capsid Proteins; D002318:Cardiovascular Diseases / Q000517:prevention & control*; D002460:Cell Line; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D051379:Mice; D009924:Organ Culture Techniques; D011296:Prenatal Diagnosis; D051381:Rats; D011993:Recombinant Fusion Proteins; D012703:Serotyping; D023822:Tissue Engineering; D014765:Viral Vaccines
D036022:Capsid Proteins; D011993:Recombinant Fusion Proteins; D014765:Viral Vaccines; C018315:hexon capsid protein, Adenovirus