Gene therapy has revolutionized the field of medical research by offering potential treatments for genetic disorders and diseases previously considered untreatable or incurable. A key aspect of gene therapy involves utilizing viral vectors, which are modified viruses that can effectively deliver therapeutic genes to target cells. How are viruses used in gene therapy? In more ways than one! Several types of viruses, including retroviruses, adenoviruses, adeno-associated viruses, and herpesviruses, have been extensively studied and adapted for use in innovative gene therapies. And because viral vectors can offer precise and efficient gene therapy delivery, they hold significant promise for treating a wide range of conditions, from inherited genetic conditions to cancer.
How Are Viruses Used in Gene Therapy?
Vectors in gene therapy can be sorted into three broad categories: engineered vectors, non-viral vectors, and viral vectors. Today, we’re going to focus on viral vectors.
Viral vectors are genetically engineered viruses that deliver foreign genetic material into cells using their viral genome. The viruses used are modified so that they do not trigger disease in the patient; once modified, the viral vector is either injected or administered intravenously.
Viral vectors are commonly used in gene therapy to solve a particular problem: namely, that direct insertion of genetic material or gene-editing tools into cells is not often effective. Instead, vectors — the vehicles that deliver genetic material or tools to target cells, tissues, or organs — are required.
So, how are viruses used in gene therapy?
Benefits of Viral Vectors in Gene Therapy
Viral vectors offer a number of important advantages for gene therapy. Their substantive genetic diversity, resilience to changes in the environment, and ability to mutate and survive in a range of conditions make them an ideal method for delivering targeted treatment to specific cells or tissues.
Viruses as a gene therapy delivery method have demonstrated promising results in preclinical and clinical trials. Their potential applications are far-reaching, with preclinical trials suggesting viral vectors could be effective in a range of applications, from treating neurological diseases to fighting cancer to developing vaccines.
Currently, the most common viral vectors used in gene therapy are adenoviruses (and adeno-associated viruses), retroviruses, lentiviruses, alphaviruses, and herpesviruses. Researchers are continually developing novel viral vectors to enhance gene delivery efficiency, safety, and effectiveness, as well as treatment longevity.
Adenoviruses and Adeno-Associated Viruses
Adenoviruses and adeno-associated viruses exhibit promise in gene therapy and are considered one of the most efficient viral methods of gene delivery. The most important advantage of adenoviruses is that they provide efficient transduction for most types of cells and tissues. Advantages of adeno-associated viruses include the following:
- Safe delivery of transgenes
Adeno-associated viruses have also demonstrated success as a method for treating certain types of hereditary blindness.
Retroviruses — enveloped viruses that contain two copies of the non-segmented ssRNA genome — have been found to be an effective and reliable vector system in gene therapy. A primary advantage of retroviral vectors is their ability to provide persistent gene transfer in dividing cells, making them suitable for long-term gene therapy applications.
Clinical trials have shown promise in using retroviral vectors to treat familial hemophagocytic lymphohistiocytosis-3 (FHL-3), high-grade glioma (an aggressive form of brain cancer), ovarian cancer, and a number of other cancers. Retroviruses have also been instrumental in developing vaccines for MERS-CoV and SARS-CoV-2.
Advantages particular to lentiviruses — a subset of retroviruses — include low cytotoxicity, inducible expression, and persistent gene transfer in most tissues. Lentiviruses have proven successful in several applications:
- The first gene therapy approved by the Food and Drug Administration (FDA) to treat Duchenne Muscular Dystrophy (DMD) utilizes a lentiviral vector to help restore dystrophin production in pediatric patients with the disease.
- Research shows that lentiviral-based gene therapy has the potential to treat a range of diseases and conditions, including Severe Combined Immunodeficiency (SCID-X1), Beta-Thalassemia, and Adenosine Deaminase (ADA) deficiency.
- Early clinical trials suggest that gene therapy using lentiviruses as vectors may be able to improve vision in some patients with Leber Congenital Amaurosis (LCA), a rare genetic disorder that causes infant vision loss.
- Lentiviral gene therapy has shown potential in slowing the progression of Metachromatic Leukodystrophy (MLD), a rare genetic disorder affecting the nervous system.
Modified herpesviruses and poxviruses are also being studied in preclinical trials as potential viral vectors for gene therapies. Herpesviruses, in particular, may prove successful in treating certain neurological conditions.
Poxviruses and Other Viruses
Other viruses used in various gene therapies include alphaviruses, Newcastle disease virus (NDV), Picornavirus, and poxviruses. Poxviruses are currently being used as viral vectors for melanoma-based gene therapy applications in the treatment of pancreatic, prostate, and colon cancers. Poxviruses have also demonstrated important potential in vaccine development.
Exploring Oncolytic Virus Therapy
Emerging and ongoing research points to oncolytic virotherapy as a potentially beneficial therapy for certain cancers, one that might improve treatment outcomes and eventually reduce reliance on chemotherapy and radiotherapy.
In October 2015, the first oncolytic virus therapy, talimogene laherparepvec (T-VEC) — a modified herpes simplex virus that acts on cancer cells — was approved by the FDA to treat melanoma.
In a more recent phase 2 study, T-VEC treatment was found to improve therapy responses in high-risk patients with early-stage triple-negative breast cancer (TNBC) who were undergoing neoadjuvant chemotherapy. The study’s results are promising, indicating that combining T-VEC with chemotherapy could be a safe and feasible approach for treating TNBC.
The viruses noted above offer promising opportunities for use as vectors in vaccine development, gene therapy, and oncolysis. More research is still needed to address the unique challenges and potential safety concerns that accompany each virus. But as preclinical and clinical trials continue, researchers are hopeful that these viral vectors may eventually be the key to developing more effective treatments for a wide range of diseases.
At QPS, we’re proud to have supported cell and gene therapy product development since 2003.
QPS is a GLP/GCP-compliant CRO delivering the highest grade of discovery, preclinical, and clinical drug development services. Since 1995, it has rapidly expanded from a bioanalysis shop to a full-service CRO with 1,200+ employees in the US, Europe, India, and Asia. Today, QPS offers expanded pharmaceutical contract R&D services with special expertise in neuropharmacology, DMPK, toxicology, bioanalysis, translational medicine, and all phases of clinical development. QPS has CLIA-certified and GLP-compliant laboratories ready to fast-track gene therapy, RT-qPCR/QPCR, serological assays, and vaccine development programs. An award-winning leader focused on bioanalysis and clinical trials, QPS is known for proven quality standards, technical expertise, a flexible approach to research, client satisfaction, and turnkey laboratories and facilities. For more information, visit www.qps.com or email [email protected].