Adenoviral-based vectors are derived from adenoviruses, which are non-enveloped, double-stranded DNA viruses. These vectors have become popular tools for gene delivery in gene therapy and molecular biology research due to their ability to transduce a wide range of cell types, including dividing and non-dividing cells, and their high transduction efficiency.
Key features of adenoviral-based vectors include:
- Broad tropism: Adenoviral vectors can infect a wide range of cell types, both dividing and non-dividing, making them suitable for various gene therapy applications and research studies.
- High transduction efficiency: Adenoviral vectors are highly efficient at delivering their genetic material into target cells, resulting in high levels of transgene expression.
- Episomal gene expression: Unlike retroviral vectors, adenoviral vectors do not typically integrate their genetic material into the host cell genome. Instead, the viral DNA remains episomal, which reduces the risk of insertional mutagenesis but also leads to a more transient gene expression that may be lost upon cell division.
- Large cargo capacity: Adenoviral vectors have a relatively large packaging capacity, with the ability to accommodate transgenes up to approximately 36 kilobases in size. This feature allows for the delivery of large or multiple genes.
- Immunogenicity: One major drawback of adenoviral vectors is their immunogenicity, which can induce strong immune responses against the viral components and the expressed transgene. This immune response can limit the effectiveness of the therapy, cause side effects, and reduce the possibility of re-administration.
To create an adenoviral vector, the viral genes required for replication and pathogenesis are replaced with the gene of interest, while the essential elements for packaging the viral genome and infecting target cells are retained. The resulting modified virus is replication-deficient and can deliver the transgene to the target cells without causing disease.
Adenoviral-based vectors have been used in various gene therapy applications, including cancer therapy, cardiovascular disease, and monogenic disorders. However, the immunogenicity of these vectors remains a significant challenge, and ongoing research aims to develop strategies to reduce the immune response and improve the safety and effectiveness of adenoviral-based gene therapy.