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HSV-1’s contribution as a vector for gene therapy

Nature Biotechnology volume 40, page 1316 (2022)Cite this article

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To the Editor — It was with much interest that I read the News article by Cormac Sheridan ‘Topical herpesvirus gene therapy enters final lap’, about the treatment of recessive dystrophic epidermolysis bullosa using B-VEC1 and the growing interest in HSV-1 non-replicative vectors. Despite the complexity of HSV-1, its use for gene therapy is slowly turning into reality. However, some of the statements in this article cast doubts on the efficacy and safety of HSV-1 vectors. As co-founder and CSO of EG427, a gene therapy biotech company specializing in HSV-1 vectors, I would like to expound here on why the potential of HSV-1 allows us to remain optimistic. The size and complexity of HSV-1 and the intricacy of interplay between it and a variety of host cells, far from being a disadvantage, allows intelligent vector design and favors HSV-1 vectors in smart therapeutic strategies, as compared with smaller vectors.

The article by Sheridan raises the question of how long the transgene encoded by the HSV-1 vector can be expressed in target cells. This depends to a large extent on the suppression of immediate-early gene expression2, which occurs naturally during spontaneous latency in sensory neurons3 and was exploited in phase 1 clinical trials testing of NP2, a replication-defective vector expressing pre-proenkephalin in sensory neurons to treat pain in patients with cancer4. This study demonstrated the innocuity of defective HSV-1: no serious adverse events or modifications in immune status occurred, even in individuals who were seropositive to HSV-1 at treatment initiation. The innocuity of HSV-1 vectors was confirmed by preclinical studies that demonstrated that non-replicative vector inoculation does not induce reactivation of resident latent virus genomes5. In addition, as of December 2019, the US clinical trials portal (https://clinicaltrials.gov/) has listed up to 38 clinical trials assessing the safety and effectiveness of oncolytic HSV-1 against several types of cancers6.

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Authors and Affiliations

  1. EG427 Pinpoint Gene Therapy, Paris, France

    Alberto L. Epstein

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  1. Alberto L. Epstein
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Correspondence to Alberto L. Epstein.

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Competing interests

A.L.E. is a cofounder of, is CSO of, and has an equity interest in EG427.

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Epstein, A.L. HSV-1’s contribution as a vector for gene therapy. Nat Biotechnol 40, 1316 (2022). https://doi.org/10.1038/s41587-022-01449-1

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