Chapter 12 - Antiviral Gene Therapy: Summary and Perspectives

Abstract

Antiviral gene therapy conveniently relies on use of rationally designed nucleic acids to disable replication of the pathogens. Popular targets for this therapy have been sequences encoding viral proteins and cellular host factors on which viruses depend for their replication. Therefore, availability of technologies that inactivate genes specifically, safely and effectively is crucial. Hence, discovery of RNA interference and advances in gene editing methods have been particularly important to the field. Gene transfer to induce prophylactic and therapeutic immunostimulation is also being developed to manage viral infections. Although promising, progress and ultimate success of antiviral gene therapy is dependent on several factors. These include overcoming problems that are generic to the field and influences of elements that are particular to specific viral infections. Viral and nonviral vectors (NVVs) have been used to deliver antiviral sequences, and both have advantages and drawbacks. Viral vectors are suited to delivering DNA-based expression cassettes, including immunostimulatory and virus-targeting sequences, whereas NVVs may be better applied to carrying therapeutic RNAs such as synthetic short interfering RNAs or mRNAs. Nonviral formulations are appealing because they cause limited immunostimulation, obviate mutagenic effects of DNA, and are amenable to easier dose control and large-scale synthesis. To date, encouraging results have been obtained in preclinical and clinical assessments of gene therapy against HIV-1, hepatitis B, hepatitis C, and Ebola viruses, among others. In the long term, widespread application of antiviral gene therapy will be dependent on the technology demonstrating good efficacy and advantages over other antiviral strategies. Access to appropriate material and human resources that are required for implementation of the technologies in various settings will also be important.