REVIEW: Viral Vectors in Gene Replacement Therapy

---

Ekaterina Minskaia^1,a*, Alima Galieva¹, Alexander D. Egorov¹, Roman Ivanov¹, and Alexander Karabelsky¹

¹Scientific Center of Translational Medicine, Department of Gene Therapy, Sirius University of Science and Technology, 354530 Sochi, Russia

Received April 28, 2023; Revised September 29, 2023; Accepted October 17, 2023

---

Throughout the years, several hundred million people with rare genetic disorders have been receiving only symptom management therapy. However, research and development efforts worldwide have led to the development of long-lasting, highly efficient, and safe gene therapy for a wide range of hereditary diseases. Improved viral vectors are now able to evade the preexisting immunity and more efficiently target and transduce therapeutically relevant cells, ensuring genome maintenance and expression of transgenes at the relevant levels. Hematological, ophthalmological, neurodegenerative, and metabolic therapeutic areas have witnessed successful treatment of hemophilia and muscular dystrophy, restoration of immune system in children with immunodeficiencies, and restoration of vision. This review focuses on three leading vector platforms of the past two decades: adeno-associated viruses (AAVs), adenoviruses (AdVs), and lentiviruses (LVs). Special attention is given to successful preclinical and clinical studies that have led to the approval of gene therapies: six AAV-based (Glybera® for lipoprotein lipase deficiency, Luxturna® for retinal dystrophy, Zolgensma® for spinal muscular atrophy, Upstaza® for AADC, Roctavian® for hemophilia A, and Hemgenix® for hemophilia B) and three LV-based (Libmeldy® for infantile metachromatic leukodystrophy, Zynteglo® for β-thalassemia, and Skysona® for ALD). The review also discusses the problems that arise in the development of gene therapy treatments, which, nevertheless, do not overshadow the successes of already developed gene therapies and the hope these treatments give to long-suffering patients and their families.

---

KEY WORDS: gene therapy, viral vectors, hereditary disorders, gene replacement therapy

DOI: 10.1134/S0006297923120179

---