An adenoviral vector expressing human adenovirus 5 and 3 fiber proteins for targeting heterogeneous cell populations.
Human adenovirus serotype 5 (HAdV-5) attaches to its primary receptor, the coxsackie and adenovirus receptor (CAR) as the first step of infection. However, CAR expression decreases as tumors progress, thereby diminishing the utility of HAdV-5-based vectors for cancer therapy. In contrast, many aggressive tumor cells highly express CD46, a cellular receptor for HAdV-3. We hypothesized that a mosaic HAdV vector, containing two kinds of fiber proteins, would provide extensive transduction in a heterogeneous population of tumor cells with varying expression levels of HAdV receptors. We therefore generated a fiber-mosaic HAdV vector displaying both a chimeric HAdV-3 fiber and the HAdV-5 fiber protein. We verified the structural integrity of purified viral particles and confirmed that the fiber-mosaic HAdV vector has expanded tropism. We conclude that the use of fiber-mosaic HAdV vectors is a promising approach for transducing a heterogeneous cell population with different expression levels of adenovirus receptors.
Murakami
Miho
M
Division of Human Gene Therapy, Department of Medicine, The University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Ugai
Hideyo
H
Wang
Minghui
M
Belousova
Natalya
N
Dent
Paul
P
Fisher
Paul B
PB
Glasgow
Joel N
JN
Everts
Maaike
M
Curiel
David T
DT
D000260:Adenoviruses, Human / Q000145:classification / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D016466:CHO Cells; D036022:Capsid Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D006224:Cricetinae; D003412:Cricetulus; D005822:Genetic Vectors; D006801:Humans; D011991:Receptors, Virus / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism*; D014161:Transduction, Genetic; D056189:Viral Tropism / Q000502:physiology*
D036022:Capsid Proteins; D011991:Receptors, Virus; D011993:Recombinant Fusion Proteins; C018315:hexon capsid protein, Adenovirus