Privately held Dyno Therapeutics Inc., an early stage biotech company applying artificial intelligence to gene therapy, entered a collaboration and license agreement with Spark Therapeutics Inc. that could bring Dyno milestone payments exceeding $1.8 billion.

Dyno will design adeno-associated virus (AAV) vectors for developing therapies to treat CNS diseases and liver-directed therapies for Spark and Roche Holding AG. Spark is a member of the Roche Group. Roche and Spark Therapeutics will conduct the preclinical, clinical and commercialization activities using capsids created by Dyno.

Dyno will receive an undisclosed up-front payment and could receive additional payments during the research phase plus clinical and sales milestone payments and royalties for products emerging from the collaboration. The aggregate value of Dyno’s future milestone payments could top $1.8 billion.

Cambridge, Mass.-based Dyno’s approach to capsid engineering emerged from the lab of co-founder George Church at the Wyss Institute in Harvard Medical School. Dyno uses large-scale DNA synthesis to generate synthetic capsid libraries containing more viable capsids than those generated by random mutagenesis. Each capsid carries its own DNA barcode to simultaneously evaluate performance of multiple capsids in pooled experiments.

AAV vectors are used in many gene therapy applications because of their safety, ability to transfect quiescent and dividing cells and also because of their relatively low immunogenicity. The technology has been validated by the regulatory approvals of an AAV-2-based gene therapy, Luxturna (voretigene neparvovec-rzyl), in certain forms of retinal dystrophy, and of Zolgensma.

Their shortcomings include limited payload size, suboptimal transduction efficiencies and limited tissue targeting capabilities.

Dyno has been busy lately cutting deals with other companies. In May, Cambridge, Mass.-based Sarepta Inc. and Dyno said they would collaborate to develop next-generation adeno-associated virus (AAV) vectors for muscle diseases, using its Capsidmap platform. The technology will be used for the design and discovery of AAV capsids with improved functional properties for gene therapy, and Sarepta will be responsible for conducting preclinical, clinical and commercialization activities for gene therapy product candidates using those capsids.

Also in May, Dyno said it would collaborate with Novartis AG to develop AAV vectors for R&D and commercialization of gene therapies for ocular disease. Terms were not specified, but Dyno said it would receive up-front consideration, research funding and license fees. The company is also set to receive clinical, regulatory and ales milestone payments along with worldwide net sales royalties on any products the partnership develops.