Novel adenovirus vectors 'capsid-displaying' a human complement inhibitor.
Adenovirus (Ad) vectors are currently the most commonly utilized gene transfer vectors in humans worldwide. Unfortunately, upon contact with the circulatory system, Ads induce several, innate, complement-dependent toxicities that limit the full potential for Ad-based gene transfer applications. Therefore, we have constructed several novel Ad5-based vectors, 'capsid-displaying' as fiber or pIX fusion proteins, a complement-regulatory peptide (COMPinh). These novel Ads dramatically minimize Ad-dependent activation of the human and non-human primate complement systems, as determined by several assays. In summary, our work has shown that a novel COMPinh-displaying Ad5 has the potential for broadening the safe use of Ad vectors in future human applications.
Seregin
Sergey S
SS
Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48823, USA.
Hartman
Zachary C
ZC
Appledorn
Daniel M
DM
Godbehere
Sarah
S
Jiang
Haixiang
H
Frank
Michael M
MM
Amalfitano
Andrea
A
D000260:Adenoviruses, Human / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D002213:Capsid / Q000378:metabolism*; D036022:Capsid Proteins / Q000235:genetics / Q000378:metabolism; D003167:Complement Activation / Q000187:drug effects; D051056:Complement Inactivating Agents / Q000378:metabolism*; D003170:Complement Pathway, Alternative; D003165:Complement System Proteins / Q000187:drug effects; D005822:Genetic Vectors; D006801:Humans; D007113:Immunity, Innate; D010455:Peptides / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014161:Transduction, Genetic
D036022:Capsid Proteins; D051056:Complement Inactivating Agents; D010455:Peptides; D011993:Recombinant Fusion Proteins; D003165:Complement System Proteins