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Recent Advances in Preclinical Developments Using Adenovirus Hybrid Vectors
Eric Ehrke-Schulz1, Wenli Zhang1, Jian Gao1
1Chair for Virology and Microbiology, Center for Biomedical Education and Research (ZBAF), Department for Human Medicine, Faculty of Health, Witten/Herdecke University , Witten, Germany .
Human Gene Therapy
|September 1, 2017
Summary
Adenovirus vectors offer efficient gene delivery but require integration for sustained expression. Hybrid vectors combine adenoviral delivery with gene editing or transposon systems for long-term therapeutic effects.
Area of Science:
- Gene Therapy
- Molecular Biology
- Virology
Background:
- Adenovirus (Ad)-based vectors are effective gene-transfer tools with large capacity and low toxicity.
- Limited integration of Ad genomes into host cells leads to decreased gene expression in dividing tissues.
- Sustained therapeutic effects necessitate strategies for long-term DNA maintenance.
Purpose of the Study:
- To review recent preclinical advancements in hybrid Adenovirus vectors (AdVs) for gene therapy.
- To explore strategies for achieving long-term gene expression and therapeutic outcomes.
- To discuss the potential of optimized hybrid AdVs for future clinical applications.
Main Methods:
- Review of preclinical studies on hybrid Adenovirus vectors.
- Characterization of Adenovirus vectors combined with Sleeping Beauty transposase system for somatic integration.
- Evaluation of Adenovirus vectors utilizing designer nucleases (TALENs, CRISPR-Cas9) for gene editing.
Main Results:
- Hybrid AdVs demonstrate potential for stable gene transfer and long-term expression.
- Somatic integration via Sleeping Beauty transposase offers a strategy for sustained gene delivery.
- Designer nucleases enable permanent gene editing for enhanced therapeutic efficacy.
Conclusions:
- Hybrid Adenovirus vectors represent a promising advancement in gene therapy.
- Combining Adenovirus with integration or gene editing technologies overcomes limitations of transient expression.
- Further optimization of these versatile tools may pave the way for clinical translation.
