What are the challenges of using viral vectors for therapeutic applications?
Viral vectors have much potential for inducing therapeutic gene transfer. However, their usage for the treatment of disease faces several significant obstacles. The biggest of these is managing the immune response. Viruses, as pathogens, are naturally immunogenic – and so are virus-infected cells. While researchers have taken steps to reduce the immunogenicity of viral vectors, they can still induce significant immune responses which not only reduce vector penetration and treatment efficacy, but can also have severe health consequences.1
Additionally, while wild-type viruses are rather selective in which cells they infect, recombinant viral vectors can have greatly expanded transduction ranges. This is a double-edged sword, as increased transduction can elevate gene transfer efficiency, but non-specific transduction can decrease the titer available at the intended site and elicit side-effects such as immune activation.1
Finally, some viral vectors integrate their genomes into existing cellular genomes, creating a risk of oncogenesis if these gene insertions disrupt existing cancer-linked genes. The incorporation of “suicide genes” – genes designed to terminate cancer cells – and developing targeted gene insertion strategies are potential methods to alleviate this risk.1
Reference:
1. C.E. Thomas, et al., “Progress and problems with the use of viral vectors for gene therapy,” Nat Rev Genet 4(5): 346-358, 2003.
Additionally, while wild-type viruses are rather selective in which cells they infect, recombinant viral vectors can have greatly expanded transduction ranges. This is a double-edged sword, as increased transduction can elevate gene transfer efficiency, but non-specific transduction can decrease the titer available at the intended site and elicit side-effects such as immune activation.1
Finally, some viral vectors integrate their genomes into existing cellular genomes, creating a risk of oncogenesis if these gene insertions disrupt existing cancer-linked genes. The incorporation of “suicide genes” – genes designed to terminate cancer cells – and developing targeted gene insertion strategies are potential methods to alleviate this risk.1
Reference:
1. C.E. Thomas, et al., “Progress and problems with the use of viral vectors for gene therapy,” Nat Rev Genet 4(5): 346-358, 2003.
