Abstract |
Vector dissemination, transient gene expression, and rapid clearance are major obstacles to successful human gene therapy. In this study, we investigated the effect of silk-elastinlike protein polymer ( SELP) hydrogels on biodistribution and anticancer efficacy of adenoviral gene therapy in a head and neck cancer model. Transcriptional activities of adenovirus carrying beta-galactosidase (Ad-LacZ) and luciferase (Ad-Luc) reporter genes were evaluated in (nu/nu) mice with head and neck cancer as a function of polymer concentration. Antitumor efficacy of thymidine kinase encoding adenovirus (Ad-Tk) and ganciclovir (GSV) combination was also evaluated. SELP (4 wt %) matrices localized viral release, minimized dissemination to liver, and enhanced reporter gene expression levels by 4-8-fold compared to virus alone. SELP- Ad-Tk with GSV reduced tumor volume significantly compared to the virus alone. SELPs provide a means for temporal and spatial control of viral gene delivery to head and neck tumors.
|
Authors | Khaled Greish, Koji Araki, Daqing Li, Bert W O'Malley Jr, Ramesh Dandu, Jordan Frandsen, Joseph Cappello, Hamidreza Ghandehari |
Journal | Biomacromolecules
(Biomacromolecules)
Vol. 10
Issue 8
Pg. 2183-8
(Aug 10 2009)
ISSN: 1526-4602 [Electronic] United States |
PMID | 19722557
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Drug Carriers
- Hydrogels
- Polymers
- Recombinant Fusion Proteins
- silk-elastinlike protein 47K
- Thymidine Kinase
- beta-Galactosidase
|
Topics |
- Adenoviridae
(genetics)
- Animals
- Drug Carriers
- Genetic Therapy
- Head and Neck Neoplasms
(genetics, therapy)
- Humans
- Hydrogels
(chemistry)
- Luminescent Measurements
- Mice
- Mice, Nude
- Polymers
(chemistry)
- Recombinant Fusion Proteins
(chemistry)
- Thymidine Kinase
(metabolism)
- Tumor Cells, Cultured
- Xenograft Model Antitumor Assays
- beta-Galactosidase
(metabolism)
|