Emerging Adenoviral Vectors for Stable Correction of Genetic Disorders
Abstract
Recent drawbacks in treating patients with severe combined immunodeficiency disorders with retroviral vectors underline the importance of generating novel tools for stable transduction of mammalian cells. Substantial progress has been made over the recent years which may offer important steps towards stable and more importantly safer correction of genetic diseases. This article discusses recent advances for stable transduction of target cells based on adenoviral gene transfer. There is accumulating evidence that recombinant adenoviral vectors (AdVs) based on various human serotypes with a broad cellular tropism and adenoviruses (Ads) from different species will play an important role in future gene therapy applications. In combination with recombinant AdVs for somatic integration these gene transfer vectors offer high transduction efficiencies with potentially safer integration patterns. Other approaches for persistent transgene expression include excision of stable episomes from the adenoviral vector genome, but also long-term persistence of the complete adenoviral vector genome as an episomal DNA molecule was demonstrated and exemplified by the treatment of various genetic diseases in small and large animal models. This review displays advantages but also limitations of these Ad based vector systems. This is the perfect time to pursue such approaches because alternative strategies for stable transduction of mammalian cells undergoing many cell divisions are urgently needed. Looking into the future, we believe that a combination of different components from different viral vectors in concert with non-viral vector systems will be successful in designing significantly optimized transfer vehicles for a broad range of different genetic diseases.
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“monly used to date [156].”
Method
- Authors
- Jager, L., & Ehrhardt, A.
- Affiliations
- Max-von-Pettenkofer-Institut für Hygiene und Medizinische Mikrobiologie (DE)
- Corresponding author
- Anja Ehrhardt
- ORCID
- Anja Ehrhardt
- Venue
- Current Gene Therapy
- Publisher
- Bentham Science Publishers Ltd.
- Published
- 2007-08-01
- Volume
- 7
- Issue
- 4
- Pages
- 272-283
- ISSN
- 1566-5232 (ISSN-L)
- OpenAlex
- W2043276804
- Cited by
- 57
- References
- 0
- Citations by year
- 2022: 2 · 2021: 3 · 2020: 4 · 2019: 1 · 2016: 1 · 2015: 2 · 2014: 2 · 2013: 7 · 2012: 5
- FWCI
- 4.46
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Gene Therapy (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Viral Infectious Diseases and Gene Expression in Insects
- Keywords
- adenoviral vector, stable transduction, gene therapy, severe combined immunodeficiency, episomal DNA, persistent transgene expression, somatic integration, non-viral vectors, genetic disorders
- MeSH terms
- Dependovirus, Adenoviridae, Adenoviruses, Human, Animals, Genetic Vectors, Humans, Plasmids, Recombination, Genetic, Serotyping, Transduction, Genetic, Genetic Therapy, Gene Expression, Genome, Viral, Genetic Diseases, Inborn
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