Combination of adeno-associated virus and adenovirus vectors expressing bone morphogenetic protein-2 produces enhanced osteogenic activity in immunocompetent rats.
We have previously shown that gene therapy using adeno-associated virus (AAV) carrying bone morphogenetic proteins (BMPs) is a promising strategy for new bone formation in vivo in SD rats. However, it had a relatively low transduction efficiency. We investigate here whether enhanced osteogenic activity can be achieved without eliciting a severe immune response, using a cocktail of AAV-BMP2 and adenovirus (Ad)-BMP2 as a vector system. The muscles of SD rats were injected with either AAV-BMP2, Ad-BMP2, or an AAV-BMP2/Ad-BMP2 cocktail, and the in vivo bone formation was determined at eight weeks post-injection. Radiographic examination demonstrated that the addition of a low level of Ad-BMP2 to AAV-BMP2 produced significantly higher new bone formation than the use of AAV-BMP2 alone. Histological and immunohistological analysis revealed an enlarged bone-forming area and a long-term BMP2 expression, without pronounced infiltration of lymphocytes. Our results provide the first evidence that the introduction of a low level of adenovirus in vivo in immunocompetent subjects can greatly enhance AAV-mediated gene transfer, without inducing severe immune responses. This cocktail vector system may offer an attractive way of improving the efficiency of AAV-based gene delivery.
Chen
Yan
Y
Department of Orthopaedics, Affiliated Hospital of Medical College, Qingdao University, China.
Luk
Keith D K
KD
Cheung
Kenneth M C
KM
Lu
William W
WW
An
Xiao-meng
XM
Ng
Samuel S M
SS
Lin
Marie C
MC
Kung
Hsiang-fu
HF
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D001846:Bone Development; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000235:genetics*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D000229:Dependovirus / Q000235:genetics*; D005822:Genetic Vectors; D007121:Immunocompetence; D007150:Immunohistochemistry; D008297:Male; D010012:Osteogenesis / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta
C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D016212:Transforming Growth Factor beta