A new era of in vivo gene therapy: the applicability of a differentiated HSV-1 based vector platform for redosable medicines

Viral vector-based gene replacement approaches have traditionally focused on the use of adenoviruses, adeno-associated viruses, and lentiviruses for functional gene transmission. Innovation in payload delivery is critical for advancing the boundaries of genetic medicine. While underappreciated, herpes simplex virus type 1 (HSV-1) possesses a number of natural traits that make it an attractive alternative for gene therapy approaches, including episomal delivery, large payload capacity, a broad tissue tropism, and the ability to resist immune clearance via inhibition of innate and adaptive anti-viral immunity. Krystal Biotech has created a proprietary HSV-1-based gene delivery platform leveraging many of the natural properties innate to HSV-1, while engineering it to be replication-incompetent to reduce cytotoxicity. This platform has been validated clinically in dermatology, and its utility is being extended into programs across additional tissue types and organ systems, including initiation of a genetic pulmonary program in cystic fibrosis. This differentiated vector platform provides a broadly applicable, highly versatile gene delivery system for the development of direct and redosable genetically-coded medicines.