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Combined Genetic and Chemical Capsid Modifications of Adenovirus-Based Gene Transfer Vectors for Shielding and Targeting
Published on: October 26, 2018
Delivery systems for enhancing oncolytic adenoviruses efficacy
Yu-Cheng Zhou1, You-Ni Zhang2, Xue Yang3
1Gastroenterological & Pancreatic Surgery Department, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou 310014, Zhejiang Province, China; Key Laboratory of Gastroenterology of Zhejiang Province, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou 310014, Zhejiang Province, China.
Abstract:
Oncolytic adenovirus (OAds) has long been considered a promising biotherapeutic agent against various types of cancer owing to selectively replicate in and lyse cancer cells, while remaining dormant in healthy cells. In the last years, multiple (pre)clinical studies using genetic engineering technologies enhanced OAds anti-tumor effects in a broad range of cancers. However, poor targeting delivery, tropism toward healthy tissues, low-level expression of Ad receptors on tumor cells, and pre-existing neutralizing antibodies are major hurdles for systemic administration of OAds. Different vehicles have been developed for addressing these obstacles, such as stem cells, nanoparticles (NPs) and shielding polymers, extracellular vesicles (EVs), hydrogels, and microparticles (MPs). These carriers can enhance the therapeutic efficacy of OVs through enhancing transfection, circulatory longevity, cellular interactions, specific targeting, and immune responses against cancer. In this paper, we reviewed adenovirus structure and biology, different types of OAds, and the efficacy of different carriers in systemic administration of OAds.
Insights
Oncolytic adenoviruses (OAds) show cancer-fighting potential but face delivery challenges. Various carriers like nanoparticles and extracellular vesicles are being explored to improve their systemic administration and anti-tumor efficacy.
Area of Science:
- Oncolytic virotherapy
- Cancer biology
- Biotechnology
Background:
- Oncolytic adenoviruses (OAds) selectively target and destroy cancer cells.
- Genetic engineering has improved OAd anti-tumor effects.
- Systemic OAd delivery faces hurdles: poor targeting, healthy tissue tropism, low Ad receptor expression, and pre-existing antibodies.
Purpose of the Study:
- To review adenovirus structure and biology.
- To discuss different types of OAds.
- To evaluate the efficacy of various carriers for OAd systemic administration.
Main Methods:
- Literature review of OAd research.
- Analysis of different carrier systems for OAds.
- Examination of OAd structure, biology, and therapeutic applications.
Main Results:
- OAds offer a promising approach to cancer treatment.
- Various carriers (stem cells, NPs, EVs, hydrogels, MPs) enhance OAd efficacy.
- These carriers improve transfection, longevity, targeting, and immune response.
Conclusions:
- Effective systemic delivery of OAds is crucial for maximizing their therapeutic potential.
- Carrier-mediated delivery systems are key to overcoming OAd administration challenges.
- Further research into optimized carrier strategies will advance oncolytic virotherapy.
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