Viral vectors are common tools used in gene therapy due to their natural ability to infect cells and integrate their genetic material. Each type of viral vector has its unique features, advantages, and limitations. Here are the main types of viral vectors used for liver transfection:
- Adenoviruses: Adenoviruses have a large capacity for foreign genes and can infect both dividing and non-dividing cells. However, they do not integrate into the host genome, so their effects are temporary. They can also induce strong immune responses, which can limit their effectiveness and cause side effects.
- Adeno-associated viruses (AAVs): AAVs can infect both dividing and non-dividing cells and do not cause any known diseases in humans, making them particularly attractive for gene therapy. Different serotypes of AAV have different tissue tropisms. AAV serotype 8 (AAV8) and AAV serotype 9 (AAV9) are commonly used for liver targeting due to their natural tropism for hepatocytes. AAVs can lead to long-term gene expression, but their cargo capacity is relatively small (about 4.7 kilobases).
- Lentiviruses: Lentiviruses, a type of retrovirus, can integrate their genetic material into the host genome, leading to permanent gene expression. They can infect both dividing and non-dividing cells and have a moderately large cargo capacity. However, their integration can sometimes cause insertional mutagenesis, which can potentially lead to cancer.
- Retroviruses: Like lentiviruses, retroviruses also integrate into the host genome. However, they can only infect dividing cells, which limits their use in some contexts. They also have the potential to cause insertional mutagenesis.
- Herpes simplex viruses (HSVs): HSVs have a very large cargo capacity and can infect a wide range of cell types. However, they can also induce immune responses and may cause cytotoxicity.
In choosing a viral vector for liver transfection, researchers need to consider the nature of the disease, the patient’s immune status, and the requirements of the therapy, such as the size of the gene to be delivered, the need for temporary or permanent expression, and the potential for off-target effects.