Precision BioSciences (DTIL) investor relations material

Advances in genome editing technologies

• Recent years have seen significant progress in protein engineering, enabling the development of non-CRISPR nucleases and optimized DNA-modifying enzymes for broader genome editing applications.

• New gene editing platforms, such as Arcus and engineered recombinases, offer alternatives to CRISPR, with unique features for precise DNA recognition and cutting.

• These technologies are being leveraged for gene insertion, large genomic changes, and targeting viral genomes.

Applications and therapeutic strategies

• Gene insertion enables correction of diseases with multiple mutations by allowing large DNA fragments to be integrated at specific genomic sites.

• Safe harbor sites, such as PCSK9, are used for targeted gene insertion, minimizing risk and enabling robust, durable expression of therapeutic genes.

• Multi-gene insertions are being explored for complex diseases and advanced CAR T therapies.

• Gene insertion is particularly suited for pediatric indications and rapidly dividing tissues, ensuring long-term therapeutic effect.

Technology optimization and delivery

• Product profiles are shaped by optimizing delivery modalities, nuclease/recombinase choice, insertion site, and construct design.

• Approaches include using AAV or LNPs for delivery, with strategies for repeat dosing and decoupling donor DNA from editing enzymes.

• Arcus nucleases enable high-efficiency gene insertion in both dividing and non-dividing cells, with the ability to insert and remove DNA in a single step.