When Adrian Wolfson was head of research and development at Sangamo, he started thinking about starting his own company. his goal? Solve some of the major challenges of genomic medicine he saw while working on a wide range of Sangamo software.
Then he met Lachlan McKinnon, a biotech investor, in London, and the two realized they shared a similar vision, despite their “orthogonal” backgrounds, he said. Endpoint news.
Replay, the new hub-and-spoke startup, is looking to change the way gene therapies are conducted. With $55 million in seed money, the biotech has amassed a series of platforms, including the HSV vector, protein rewriting algorithm and DNA writing tool from George Church Laboratory.
“We have basically identified three major challenges that we are solving, which we believe will define the future,” said Wolfson, Chairman and President. The first being the load capacity; The second is the need for a ready-to-use, low-cost, scalable cell therapy platform with large-scale genetic design; The third is the ability to synthesize large DNA.”
Replay’s primary technology is the HSV Delivery System. While AAV vectors can generally contain only about 4.7 kbase of a gene, HSV vectors can contain about 150 kbase. With this increased capacity, therapies that use the viral vector could extend to diseases with larger genes, such as muscular dystrophy, and genes with introns (and regulatory parts) intact, Wolfson noted.
Wolfson added that Replay contains two classes of HSV vectors. “We have the herpes simplex virus that is gene-deleted, but we also have what we call an amplicon — which is HSV where we have stripped almost all of the genes — and this is an almost non-viral vector,” Wolfson said. “And we think that would actually be the most convincing of all.”
However, the jury is still not sure whether a treatment based on herpes simplex virus would be safer than standard AAV treatment, in which the viral vector causes a dangerous immune response. Wolfson admitted that as with AAV, the body has neutralizing antibodies against the herpes simplex virus, although he added that the herpes simplex virus has evolved to better evade the immune system.
A range of biotechnologies has grown out of efforts to solve various problems related to gene therapies. SpliceBio attempts to solve payload limitations through protein splicing, and Apertura is working on custom-built AAV vectors that hope to get AAVs into hard-to-reach areas.
Replay has also licensed DNA writing technology, which is used to build synthetic strands of DNA. “We believe we can summarize what we see through DNA sequencing and significantly reduce the cost of writing to help pioneer a new era in genome writing,” Wolfson said.
To date, the platform company has founded five different product companies — four HSV gene therapy companies focused on single-gene disorders, including one for Parkinson’s disease and one for Duchenne muscular dystrophy, and one enzyme-writing company.
KKR and OMX Ventures led the Replay seed tour, which also included ARTIS Ventures, Lansdowne Partners, SALT, DeciBio Ventures and Axial.