Krystal’s Engineered Replication Deficient HSV-1 Platform

Krystal’s engineered replication deficient HSV-1–based platform enables the development of redosable gene therapies that can be administered non- or minimally‑invasively.

The platform is based on a differentiated viral vector system that leverages many of HSV-1’s natural properties, including episomal delivery, a high payload capacity, broad tropism, and inherent evasion of the immune system, while being engineered to be replication incompetent to reduce cytotoxicity.

HSV-1 Illustration

Unique Properties of HSV-1

1

Large genetic payload capacity well in excess of other viral vectors

HSV-1 is a relatively complex virus with a large genome. The theoretical cargo capacity > 30 kb significantly exceeds the capacity of AAV (<5 kb) and lentiviruses (9 kb); VYJUVEK contains over 19 kb of genetic cargo.

2

Efficient transduction of wide range of cell types

HSV-1 employs multiple mechanisms to gain cell entry and majority of cell types are permissive; Krystal vectors shown to transduce keratinocytes, fibroblasts, and various cells of the eye and lung so far.

3

Evades host immunity allowing for repeat dosing and reducing immunotoxicity

The ability of HSV-1 to block innate and adaptive immune responses is retained in Krystal vectors; no evidence of significant or persistent neutralizing immunity after single or repeat dosing in preclinical or clinical studies to date.

4

DNA payload enables durable expression without integration risk

HSV-1 delivers its genome to the nucleus where it persists episomally; no clinical reports of integrations with parental wild‑type virus or Krystal constructs.

5

Scalable manufacturing of viral gene therapies

Capable of increasing manufacturing in a streamlined manner because of in-house capabilities.

Mechanism of Action

Discovering, developing, and commercializing genetic medicines with purpose

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