Viral Vector Systems for Gene Therapy: A Comprehensive Literature Review of Progress and Biosafety Challenges

Abstract

Introduction: National Institutes of Health (NIH) defines gene therapy as an experimental technique that uses genes to treat or prevent disease. Although gene therapy is a promising treatment option for a number of diseases (including inherited disorders, some types of cancer, and certain viral infections), the technique remains risky and is still under study to make sure that it will be effective and safe. Methods: Applications of viral vectors and nonviral gene delivery systems have found an encouraging new beginning in gene therapy in recent years. Although several viral vectors and nonviral gene delivery systems have been developed in the past 3 decades, no one delivery system can be applied in gene therapy to all cell types in vitro and in vivo. Furthermore, the use of viral vector systems (both in vitro and in vivo) present unique occupational health and safety challenges. In this review article, we discuss the biosafety challenges and the current framework of risk assessment for working with the viral vector systems. Discussion: The recent advances in the field of gene therapy is exciting, but it is important for scientists, institutional biosafety committees, and biosafety officers to safeguard public trust in the use of this technology in clinical trials and make conscious efforts to engage the public through ongoing forums and discussions.

Safeguards for Using Viral Vector Systems in Human Gene Therapy: A Resource for Biosafety Professionals Mitigating Risks in Health Care Settings

“…[3][4][5] As of 2020, more than 2900 gene therapy clinical trial studies have been initiated worldwide. 3,4,6 A search in the ClinicalTrials.gov webpage with the keywords "gene therapy" resulted in more than 4255 studies, with more than 1000 currently recruiting or enrolling research participants. [3][4][5][6] Bracing for a massive upsurge in the development of cell and gene therapies, the Food and Drug Administration (FDA) expects to receive up to 200 new applications every year from 2020 to start trials.…”

“…3,4,6 A search in the ClinicalTrials.gov webpage with the keywords "gene therapy" resulted in more than 4255 studies, with more than 1000 currently recruiting or enrolling research participants. [3][4][5][6] Bracing for a massive upsurge in the development of cell and gene therapies, the Food and Drug Administration (FDA) expects to receive up to 200 new applications every year from 2020 to start trials. 3,4,6 The FDA also expects to be approving 10 to 20 cell and gene therapies every year from 2025, reflecting a turning point in the development of these technologies and their application to human health.…”

“…[3][4][5][6] Bracing for a massive upsurge in the development of cell and gene therapies, the Food and Drug Administration (FDA) expects to receive up to 200 new applications every year from 2020 to start trials. 3,4,6 The FDA also expects to be approving 10 to 20 cell and gene therapies every year from 2025, reflecting a turning point in the development of these technologies and their application to human health. 3,7 The FDA issued its first recombinant DNA product approval in 2015 and has since approved 6 more products, the most recent being Zolgensma in May 2019.…”

“…3,7 The FDA issued its first recombinant DNA product approval in 2015 and has since approved 6 more products, the most recent being Zolgensma in May 2019. 3,6 With 291 gene therapy studies currently in Phase III clinical trials (with up to 3000 participants), several more gene therapy products will likely be considered for approval in the coming years. 3,4,7 Most of these gene therapy products are viral vector system based.…”

“…1,13 However, some viral vector systems remain risky and are still under study to ensure safety and efficacy during clinical trials. 6 Viruses used for gene delivery systems include retrovirus, adenovirus, adeno-associated viruses, and herpes simplex viruses. 2,14 Additionally, vector types represent both RNA and DNA viruses with either single-stranded (ss) or double-stranded (ds) genomes.…”