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Production and Purification of Non Replicative Canine Adenovirus Type 2 Derived Vectors
Published on: December 3, 2013
Transductional targeting of adenovirus vectors for gene therapy
J N Glasgow1, M Everts, D T Curiel
1Division of Human Gene Therapy, Department of Medicine, Birmingham, AL 35294, USA.
Abstract:
Cancer gene therapy approaches will derive considerable benefit from adenovirus (Ad) vectors capable of self-directed localization to neoplastic disease or immunomodulatory targets in vivo. The ablation of native Ad tropism coupled with active targeting modalities has demonstrated that innate gene delivery efficiency may be retained while circumventing Ad dependence on its primary cellular receptor, the coxsackie and Ad receptor. Herein, we describe advances in Ad targeting that are predicated on a fundamental understanding of vector/cell interplay. Further, we propose strategies by which existing paradigms, such as nanotechnology, may be combined with Ad vectors to form advanced delivery vehicles with multiple functions.
Insights
Adenovirus (Ad) vectors for cancer gene therapy can be engineered for targeted delivery, improving efficiency by overcoming reliance on natural cell receptors. Combining Ad vectors with nanotechnology offers advanced, multifunctional delivery systems.
Area of Science:
- Biotechnology and Biomedical Engineering
- Oncology and Gene Therapy
Background:
- Adenovirus (Ad) vectors are crucial for cancer gene therapy but face challenges with targeted delivery.
- Native Ad tropism relies on specific cellular receptors, limiting precise localization in vivo.
- Overcoming Ad dependence on native receptors is key to enhancing therapeutic efficacy.
Purpose of the Study:
- To explore advances in adenovirus vector targeting for cancer gene therapy.
- To demonstrate methods for ablating native Ad tropism while retaining gene delivery efficiency.
- To propose strategies for creating advanced, multifunctional Ad-based delivery vehicles.
Main Methods:
- Engineering adenovirus vectors to ablate native tropism.
- Implementing active targeting modalities for directed localization.
- Investigating vector/cell interplay for fundamental understanding of targeting mechanisms.
- Integrating nanotechnology with adenovirus vectors.
Main Results:
- Successful ablation of native Ad tropism while maintaining gene delivery efficiency.
- Demonstrated circumvention of Ad dependence on the coxsackie and Ad receptor.
- Advances in Ad targeting based on a fundamental understanding of vector/cell interactions.
Conclusions:
- Engineered adenovirus vectors offer significant benefits for cancer gene therapy through targeted delivery.
- Targeting strategies can overcome natural tropism limitations, enhancing therapeutic potential.
- Combining adenovirus vectors with nanotechnology can create advanced, multifunctional delivery systems for future applications.
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