Retargeted adenoviruses for radiation-guided gene delivery

Autor: Sergey A. Kaliberov, Heping Yan, Vaishali Kapoor, Dennis E. Hallahan, Lyudmila N. Kaliberova
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
Cancer Research
Genetic enhancement
Genetic Vectors
Gene Expression
Gene delivery
Biology
Adenoviridae
03 medical and health sciences
Mice
0302 clinical medicine
Antigens
Neoplasm
Genes
Reporter
Transduction
Genetic
Glioma
Cell Line
Tumor
Radiation
Ionizing
Gene expression
medicine
Animals
Humans
Receptors
Vitronectin
Transgenes
Molecular Biology
Endoplasmic Reticulum Chaperone BiP
Heat-Shock Proteins
Oncolytic Virotherapy
Reporter gene
X-Rays
Gene Transfer Techniques
Genetic Therapy
medicine.disease
Integrin alphaVbeta3
Molecular biology
Xenograft Model Antitumor Assays
In vitro
3. Good health
Oncolytic virus
Disease Models
Animal
Oncolytic Viruses
030104 developmental biology
030220 oncology & carcinogenesis
Cancer cell
Cancer research
Molecular Medicine
Original Article
Capsid Proteins
Female
Zdroj: Cancer Gene Therapy
ISSN: 1476-5500
0929-1903
Popis: The combination of radiation with radiosensitizing gene delivery or oncolytic viruses promises to provide an advantage that could improve the therapeutic results for glioblastoma. X-rays can induce significant molecular changes in cancer cells. We isolated the GIRLRG peptide that binds to radiation-inducible 78 kDa glucose-regulated protein (GRP78), which is overexpressed on the plasma membranes of irradiated cancer cells and tumor-associated microvascular endothelial cells. The goal of our study was to improve tumor-specific adenovirus-mediated gene delivery by selectively targeting the adenovirus binding to this radiation-inducible protein. We employed an adenoviral fiber replacement approach to conduct a study of the targeting utility of GRP78-binding peptide. We have developed fiber-modified adenoviruses encoding the GRP78-binding peptide inserted into the fiber-fibritin. We have evaluated the reporter gene expression of fiber-modified adenoviruses in vitro using a panel of glioma cells and a human D54MG tumor xenograft model. The obtained results demonstrated that employment of the GRP78-binding peptide resulted in increased gene expression in irradiated tumors following infection with fiber-modified adenoviruses, compared with untreated tumor cells. These studies demonstrate the feasibility of adenoviral retargeting using the GRP78-binding peptide that selectively recognizes tumor cells responding to radiation treatment.
Databáze: OpenAIRE
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