Viral vectors are a crucial tool within the advanced therapy sector, providing an elegant solution for gene delivery in areas such as gene therapy and vaccine development. These viral particles, often uniquely engineered for a specific application, can effectively deliver genes into target cells, sometimes even enabling long term expression of the therapeutic gene of interest. However, producing clinical grade viral vectors comes with significant challenges and cost, partly due to comparatively low productivity of viral vector expression systems, in tandem with complex and onerous downstream processes.
In this article, we review viral vectors as a tool for advancing novel medicinal products and investigate the key steps and main challenges of viral vector purification. Finally, we will explore some of the emerging trends that hold the potential to transform access to advanced therapies.
Viral Vectors: The Essentials of Advanced Therapies
In the decades since their discovery, many viral vectors have been developed for gene delivery in vitro, however, only a small subset of these have been established as safe for therapeutic use, including:
• Adeno-associated Viruses (AAVs): AAVs are non-pathogenic and can integrate into the host genome, offering long-term gene expression.
• Lentiviral Vectors (LVs): Derived from HIV, LVs can infect dividing and non-dividing cells, allowing stable gene integration and expression.
• Adenoviral Vectors (Ads): Derived from Adenoviruses, these vectors can carry large DNA inserts and are effective for transient expression of genes.
• Retroviral Vectors (RVs): These vectors integrate into the host genome, but primarily infect dividing cells.
There is significant variation between these vectors in terms of efficiency, stability of gene expression and versatility. The most appropriate vector, payload and dose is largely dictated by the target therapeutic application. For gene therapy applications, integrating non-pathogenic viruses will be favourable when delivering therapeutic genes to correct genetic disorders, such as cystic fibrosis or haemophilia.
On the other hand, when looking at cancer treatment, vectors with specific tropism and activation mechanisms will be preferred in order to induce apoptosis in malignant cells. Alternatively, vectors with high integration efficiency and long-term stable expression will be used to genetically modify cells ex-vivo, before re-administrating them to the patient to elicit an immune response.
