TY - JOUR
T1 - An adenovirus vector with a chimeric fiber derived from canine adenovirus type 2 displays novel tropism
AU - Glasgow, Joel N.
AU - Kremer, Eric J.
AU - Hemminki, Akseli
AU - Siegal, Gene P.
AU - Douglas, Joanne T.
AU - Curiel, David T.
N1 - Funding Information:
This work was supported by NIH grants R01 CA93796, R01 HL67962, R01 CA86881, R01 AG021875, R01 CA090547, NIH training grant T32 CA75930, breast cancer SPORE grant P50 CA89019, the Fondation pour la Recherche Medicale, the Association pour la Recherche contre Cancer, and the Association Française contre les Myopathies. The authors thank Dr. Igor Dmitriev, Dr. Hongju Wu, Lucretia Sumerel, and Minghui Wang for invaluable technical assistance. DNA vectors pSHAFT, pNEB.PK.3.6, and pVK700 were generous gifts from Dr. Victor Krasnykh.
PY - 2004/6/20
Y1 - 2004/6/20
N2 - Many clinically relevant tissues are refractory to Ad5 transduction because of negligible levels of the primary Ad5 receptor, the coxsackie and adenovirus receptor (CAR). Thus, development of Ad vectors that display CAR-independent tropism could lead directly to therapeutic gain. The Toronto strain of canine adenovirus type 2 (CAV2) exhibits native tropism that is augmented by, but not fully dependent upon, CAR for cellular transduction. We hypothesized that an Ad5 vector containing the nonhuman CAV2 knob would provide expanded tropism and constructed Ad5Luc1-CK, an E1-deleted Ad5 vector encoding the fiber knob domain from CAV2. Ad5Luc1-CK gene delivery to CAR-deficient cells was augmented up to 30-fold versus the Ad5 control vector, and correlated with increased cell surface binding. Further, we confirmed the importance of cellular integrins to Ad5Luc1-CK transduction. Herein, we present the rationale, design, purification, and characterization of a novel tropism modified, infectivity-enhanced Ad vector.
AB - Many clinically relevant tissues are refractory to Ad5 transduction because of negligible levels of the primary Ad5 receptor, the coxsackie and adenovirus receptor (CAR). Thus, development of Ad vectors that display CAR-independent tropism could lead directly to therapeutic gain. The Toronto strain of canine adenovirus type 2 (CAV2) exhibits native tropism that is augmented by, but not fully dependent upon, CAR for cellular transduction. We hypothesized that an Ad5 vector containing the nonhuman CAV2 knob would provide expanded tropism and constructed Ad5Luc1-CK, an E1-deleted Ad5 vector encoding the fiber knob domain from CAV2. Ad5Luc1-CK gene delivery to CAR-deficient cells was augmented up to 30-fold versus the Ad5 control vector, and correlated with increased cell surface binding. Further, we confirmed the importance of cellular integrins to Ad5Luc1-CK transduction. Herein, we present the rationale, design, purification, and characterization of a novel tropism modified, infectivity-enhanced Ad vector.
KW - Adenovirus
KW - Coxsackie and adenovirus receptor (CAR)
KW - Gene therapy
KW - Targeting
KW - Tropism modification
UR - http://www.scopus.com/inward/record.url?scp=2942528908&partnerID=8YFLogxK
U2 - 10.1016/j.virol.2004.03.028
DO - 10.1016/j.virol.2004.03.028
M3 - Article
C2 - 15183058
AN - SCOPUS:2942528908
SN - 0042-6822
VL - 324
SP - 103
EP - 116
JO - Virology
JF - Virology
IS - 1
ER -