Hear From KiraGen Bio

KiraGen Bio is pioneering a machine learning-driven approach to develop CAR-T cell therapies capable of overcoming the immunosuppressive tumor microenvironment (TME) in solid tumors, starting with glioblastoma.

KiraGen’s ambitious approach to creating more durable CAR-T cells involves knocking out multiple receptors sensing immunosuppressive pathways simultaneously. However, this introduces significant technical hurdles, including:

• Low efficiency in multiplex editing
• Billions of possible edit combinations requiring evaluation
• Inconsistent performance across different T cell populations

Given these challenges, traditional trial-and-error methods are impractical. KiraGen addresses this by leveraging a large phenotype model (LPM)- a transformer-based machine learning model trained on real biological CAR-T assay data to predict functional outcomes from synergistic combinations of gene edits, even for untested gene targets. This allows systematic prediction, screening, and optimization of only the most promising multiplex editing combinations.

GenScript’s Role in Accelerating Discovery

KiraGen Bio utilized GenScript’s custom guide RNA design and synthesis services to enable high-efficiency multiplex editing in their CAR-T programs. GenScript’s gRNA enabled the KiraGen team to:

• Efficiently achieve simultaneous five-gene knockouts using base editing.
• Rapidly validate the most effective combinations in preclinical models.

Impact & Future Directions

The collaboration has delivered:

• TME-Guard CAR-T cells with demonstrated functional resistance to immunosuppression in 3D spheroid and xenograft models
• Validation of KiraGen’s AI/ML platform for designing next-generation cell therapies more rapidly and at scale
• A critical foundation for a pipeline of tumor-resistant cell therapies that can survive and thrive within the TME.

“Overall, working with GenScript has been seamless. The turnaround times and product consistency gave us confidence to scale rapidly and present our results at ASGCT, where we highlighted how multiplex editing powered by GenScript reagents is advancing the field of solid tumor cell therapies.

We were so pleased with the quality and performance of the Genscript gRNAs that we are now in discussions to utilize Genscript as our GMP source of gRNA material as we progress towards the clinic. ”

– Ryan Murray

Why This Matters

This work demonstrates how the integration of cutting-edge gene editing strategies, AI, and reliable RUO to cGMP gRNA production can overcome longstanding barriers in cell therapy.