Abstract
Two main types of vectors can be derived from herpes simplex type 1 (HSV-1), non-replicative vectors and replication-selective oncolytic vectors. The main goal of this review is to describe the key features that make non-replicative HSV-1 vectors (nrHSV-1) extremely appealing for gene therapy of peripheral and central nerve diseases. This includes the many outstanding adaptations that this human neurotropic virus has developed to safely infect, persist, and perform long-term gene expression in neurons, their very large transgene cargo capacity, unique amongst nuclear mammalian viruses, and the very important fact that they can be readministered several times due to the extremely low levels of immunological responses they elicit. This review also describes several preclinical studies as well as the clinical trials that have been developed or are ongoing with nrHSV-1, including gene therapy of cancer-related intractable pain and of recessive dystrophic epidermolysis bullosa (RDEB), which has been recently approved by the FDA. In the second part of this review, we compare side-by-side, the advantages and the drawbacks of nrHSV-1 and adeno-associated vectors (AAV), the most currently used gene therapy vector. Lastly, we will very briefly describe oncolytic vectors and a second type of nrHSV-1 vectors known as amplicons.