An adenoviral vector is a modified virus that scientists use as a tool in research and medicine. These vectors originate from adenoviruses, common viruses that cause mild respiratory, gastrointestinal, or eye infections in humans. However, the adenoviruses are altered in the laboratory to be harmless and unable to cause disease. They are engineered to deliver genetic material into cells for various therapeutic and scientific purposes.
Engineering for Gene Delivery
A “vector” serves as a delivery vehicle for genetic material. To transform a naturally occurring adenovirus into a useful vector, scientists modify its genome. They remove certain genes, such as the E1 and E3 regions, that enable the virus to replicate and cause illness, making the vector replication-deficient. This genetic modification creates space within the viral structure to insert new, desired genetic material, such as a therapeutic gene or one designed to elicit an immune response.
The engineered adenoviral vector, carrying its new genetic material, delivers this into target cells. The virus naturally attaches to and enters cells by binding to receptors on the cell surface, such as the coxsackie-adenovirus receptor (CAR), and is then internalized. Once inside, the vector releases its double-stranded DNA genome into the cell’s nucleus. This genetic material remains as a separate entity within the nucleus, without integrating into the host cell’s chromosomes. The introduced DNA’s instructions are then transcribed and expressed by the cell’s machinery, allowing the therapeutic or desired gene to function.
Medical Applications
Adenoviral vectors are used in various medical applications, especially gene therapy. They deliver new genetic material into cells to correct genetic defects or add new functions. For example, if a person has a disease caused by a faulty gene, an adenoviral vector can carry a healthy copy into the affected cells, allowing them to produce the correct protein. This approach treats genetic disorders by providing necessary genetic instructions.
Adenoviral vectors are also used in vaccine development. They deliver genetic material from a pathogen, such as a virus, into the body’s cells. The cells then produce proteins from the pathogen, which the immune system recognizes, prompting an immune response without causing the actual disease. This mechanism is leveraged in certain viral vaccines, including some developed for COVID-19, where adenoviral vectors deliver genetic instructions for the SARS-CoV-2 spike protein to trigger immunity.
Adenoviral vectors are also explored in cancer therapies. They can be engineered to deliver genes that specifically target and destroy cancer cells. Some vectors are designed to replicate only within tumor cells, leading to their destruction through oncolytic virotherapy. Other approaches involve delivering genes that enhance the body’s immune response against tumors, teaching the immune system to recognize and attack cancer cells.
Practical Considerations
Adenoviral vectors offer several advantages for delivering genetic material. They are highly efficient in transferring genes into various cell types, including both dividing and non-dividing cells. Researchers can also produce them in large quantities with high viral titers, making them suitable for large-scale therapeutic and research needs. Their large packaging capacity, up to 8 kilobases of foreign genetic material, allows for substantial genetic payloads.
Despite these advantages, considerations exist when using adenoviral vectors. The body can mount an immune response against the vector itself. Because many people have been naturally exposed to adenoviruses, their immune systems can recognize the vector and generate antibodies. This can limit the effectiveness of repeated administrations or the duration of gene expression. This immune response can also lead to temporary inflammation or other transient side effects.
Modified adenoviral vectors are designed for safety. Removing replication-enabling genes ensures these vectors cannot multiply within the human body, reducing viral infection risk. While considered safe for human use, ongoing research refines these vectors to minimize immune reactions and improve targeting specificity for better therapeutic outcomes.