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Advanced generation adenoviral vectors possess augmented gene transfer efficiency based upon coxsackie adenovirus
V Krasnykh1, I Dmitriev, J G Navarro
1Department of Medicine, Gene Therapy Center, The University of Alabama at Birmingham, 35294-3300, USA.
Abstract:
Adenoviral (Ad) vectors have been widely used in the context of cancer gene therapy approaches. Their utility in these contexts, however, has frequently been limited by tumor cell resistance to Ad infection. The basis of this resistance has been defined recently as resulting from a deficiency of the primary adenovirus receptor, coxsackie adenovirus receptor. As a means to circumvent this limitation, a variety of tropism modification strategies have allowed coxsackie adenovirus receptor-independent gene delivery via the Ad vector. These advanced generation adenovirus vectors exhibit enhanced infectivity, which can allow direct therapeutic gain. Such vectors may allow improvements in efficacy in the context of ongoing human clinical gene therapy approaches for cancer.
Insights
Adenoviral vectors show promise for cancer gene therapy but face resistance due to low coxsackie adenovirus receptor. Modified vectors overcome this, enhancing infectivity and therapeutic potential in clinical trials.
Area of Science:
- Oncolytic virotherapy
- Gene therapy
- Adenovirus vector engineering
Background:
- Adenoviral (Ad) vectors are utilized in cancer gene therapy.
- Tumor cell resistance to Ad infection, due to deficiency of the coxsackie adenovirus receptor (CAR), limits their efficacy.
- Overcoming CAR-dependent entry is crucial for effective Ad-mediated gene delivery.
Purpose of the Study:
- To review strategies for modifying Ad vector tropism for CAR-independent gene delivery.
- To highlight the potential of advanced Ad vectors in cancer gene therapy.
Main Methods:
- Tropism modification strategies for Ad vectors.
- Engineering of advanced generation adenovirus vectors.
- Assessment of enhanced infectivity for therapeutic gain.
Main Results:
- Development of Ad vectors capable of CAR-independent infection.
- Demonstration of enhanced infectivity in modified Ad vectors.
- Potential for improved therapeutic efficacy in cancer gene therapy.
Conclusions:
- Modified Ad vectors can circumvent tumor resistance mediated by CAR deficiency.
- Advanced Ad vectors offer improved infectivity for direct therapeutic benefit.
- These vectors hold promise for enhancing efficacy in human clinical gene therapy for cancer.