Viral vector

Viral vectors exploit the natural ability of viruses to deliver nucleic acids into host cells. The viral genome is modified to remove genes essential for replication, preventing uncontrolled spread, while retaining elements that allow packaging and delivery. Common vector types include retroviruses, lentiviruses, adenoviruses, adeno-associated viruses (AAV), and herpes simplex viruses, each with distinct tropism, packaging capacity, and immunogenicity.¹

For example, lentiviral vectors integrate into the host genome, enabling long-term expression, whereas AAV vectors remain episomal, reducing insertional mutagenesis risk. Adenoviral vectors are highly immunogenic but efficient for transient expression, making them suitable for vaccines.² Production involves packaging cell lines that supply missing viral proteins in trans.

Viral vectors are central to gene therapy, with approved products such as Luxturna (AAV for inherited retinal disease) and Zolgensma (AAV for spinal muscular atrophy). They are also used in CAR-T cell therapies, where lentiviral vectors deliver chimeric antigen receptor genes into patient T cells.³

In vaccinology, viral vectors have been deployed against infectious diseases. The Ebola vaccine (rVSV-ZEBOV) and several COVID-19 vaccines, including Oxford–AstraZeneca and Johnson & Johnson, use adenoviral vectors. These vaccines induce robust humoral and cellular immunity, and can be engineered to encode antigens from multiple pathogens.

Safety concerns include immunogenicity, which can limit repeat dosing, and the risk of insertional mutagenesis with integrating vectors. In early gene therapy trials, retroviral vectors caused leukemia in several patients due to integration near oncogenes.⁴ Modern vectors are designed with safer integration profiles, and non-integrating vectors like AAV are preferred for many applications.

Immune responses to the vector capsid can neutralize the vector or cause adverse reactions, as seen with high-dose AAV therapies. Researchers are developing capsid engineering, immunosuppressive regimens, and alternative serotypes to mitigate these issues.⁵

Beyond gene therapy, viral vectors are used in neuroscience to map neural circuits, with rabies virus and adeno-associated viruses enabling retrograde and anterograde tracing.⁶ They also serve as tools for genome editing, delivering CRISPR components into cells.

Historically, the first viral vector was developed in 1968 using SV40, and early work with retroviruses in the 1980s laid the foundation for modern vectors.¹ Niche applications include using plant viruses like tobacco mosaic virus for producing therapeutic proteins in plants, and using bacteriophages for targeted drug delivery.

Transgene

The foreign gene carried by the viral vector.

Tropism

The specificity of a virus for particular cell types.

Replication-incompetent

A virus that cannot replicate in host cells due to deleted genes.