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Published Online: 28 December 2006

Differential Biodistribution of Adenoviral Vector In Vivo as Monitored by Bioluminescence Imaging and Quantitative Polymerase Chain Reaction

Publication: Human Gene Therapy
Volume 17, Issue Number 12

Abstract

A better understanding of the in vivo biodistribution of adenoviral vectors would enable the researcher to anticipate potential side effects due to off-targeted site of transduction, and aid in the strategic design of gene therapy. We combined real-time polymerase chain reaction with in vivo optical imaging to examine viral transduction in liver, lung, spleen, kidney, prostate, and lymph nodes. A replication-deficient serotype 5 adenoviral vector expressing the firefly luciferase gene under the control of a constitutive cytomegalovirus promoter was administered in vivo via different routes. Intravenous and intraperitoneal injections resulted in greatest gene expression and viral DNA in the liver, whereas intraperitoneal injections led to a greater extent of gene delivery to the prostate. Although prostate-directed injection resulted in dominant gene expression in the targeted site, leakage of the vector to other organs was also observed. Vector injection into the lymphatic-rich paw tissue or the subcutaneous tissue of shoulder or chest followed the expected lymphatic drainage pattern, resulting in the accumulation of viral vector in ipsilateral brachial and axillary lymph nodes. Collectively, this study demonstrates that each tissue retains various amounts of adenoviral vector, depending on the route of administration. This knowledge is useful in the strategic design and implementation of adenovirus-mediated gene therapies.

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cover image Human Gene Therapy
Human Gene Therapy
Volume 17Issue Number 12December 2006
Pages: 1262 - 1269
PubMed: 17117891

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Published online: 28 December 2006
Published in print: December 2006

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Mai Johnson
Department of Molecular, Cellular, and Integrative Physiology, University of California Los Angeles, Los Angeles, CA 90095.
Steve Huyn
Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA 90095.
Jeremy Burton
Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA 90095.
Makoto Sato
Department of Urology, University of California Los Angeles, Los Angeles, CA 90095.
Dr. Lily Wu
Department of Molecular, Cellular, and Integrative Physiology, Department of Molecular and Medical Pharmacology, and Department of Urology, University of California Los Angeles, Los Angeles, CA 90095.

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