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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
shRNA-armed conditionally replicative adenoviruses: a promising approach for cancer therapy
Jie Zhang1, Meng Ding1, Kai Xu1
1Jiangsu Key Laboratory of Biological Cancer Therapy, Xuzhou Medical College, Xuzhou, China.
Abstract:
The small-interfering RNAs (siRNAs) have been employed to knockdown the expression of cancer-associated genes and shown some promise in cancer therapy. However, synthetic siRNA duplexes or plasmid mediated delivery of siRNAs have several problems, such as short half-life, low transfection efficiency and cytotoxicity associated with transfection. Conditionally replicating adenovirus (CRAds) as the delivery vector for short hairpin RNAs (shRNAs) could overcome these limitations and have shown augmented anti-tumor effects in experimental studies and preclinical trials. In this review, we summarize recent progress in the development of CRAds-shRNA for cancer treatment. Combination of CRAds-shRNA with chemotherapeutics, radiation, dendritic cells, monoclonal antibodies and small-molecule inhibitors will be necessary to eradicate cancer cells and cancer stem cells and achieve superior outcomes. The use of CRAd platform for efficient delivery of shRNAs and foreign genes will open a new avenue for cancer therapy.
Insights
Conditionally replicating adenoviruses (CRAds) deliver short hairpin RNAs (shRNAs) to overcome limitations of small-interfering RNAs (siRNAs) in cancer therapy, showing promise for enhanced anti-tumor effects.
Area of Science:
- Oncology
- Gene Therapy
- Viral Vectors
Background:
- Small-interfering RNAs (siRNAs) show potential for cancer gene knockdown but face delivery challenges like short half-life and cytotoxicity.
- Current siRNA delivery methods (synthetic duplexes, plasmids) exhibit limitations impacting therapeutic efficacy.
Purpose of the Study:
- To review the progress of using conditionally replicating adenoviruses (CRAds) as vectors for short hairpin RNAs (shRNAs) in cancer treatment.
- To highlight the potential of CRAds-shRNA to overcome existing siRNA delivery obstacles.
Main Methods:
- Review of experimental studies and preclinical trials involving CRAds-shRNA.
- Analysis of combination strategies for CRAds-shRNA with other cancer therapies.
Main Results:
- CRAds-shRNA delivery overcomes limitations associated with synthetic siRNAs, demonstrating augmented anti-tumor effects.
- CRAds-shRNA platforms show promise for efficient delivery of therapeutic RNAs and foreign genes.
Conclusions:
- CRAds-shRNA represents a promising advancement in cancer gene therapy, addressing key delivery challenges.
- Combination therapies involving CRAds-shRNA with chemotherapeutics, radiation, and immunotherapies are crucial for eradicating cancer and cancer stem cells.
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